Impact of Red Wine Consumption on Cardiovascular Health

Luca        Liberale; Aldo        Bonaventura; Fabrizio        Montecucco; Franco        Dallegri; Federico        Carbone
Abstract

Background: The devastating effects of heavy alcohol drinking have been long time recognized. In the last decades, potential benefits of modest red wine drinking were suggested. In European countries in which red wide intake is not negligible (such as France), the association between cholesterol and cardiovascular (CV) risk was less evident, suggesting the action of some protective molecules in red wine or other foods and drinks.
Methods: This narrative review is based on the material searched for and obtained via PubMed up to May 2016. The search terms we used were: “red wine, cardiovascular, alcohol” in combination with “polyphenols, heart failure, infarction”.
Results: Epidemiological and mechanistic evidence of a J-shaped relationship between red wine intake and CV risk further supported the “French paradox”. Specific components of red wine both in vitro and in animal models were discovered. Polyphenols and especially resveratrol largely contribute to CV prevention mainly through antioxidant properties. They exert beneficial effects on endothelial dysfunction and hypertension, dyslipidemia, metabolic diseases, thus reducing the risk of adverse CV events such as myocardial infarction ischemic stroke and heart failure. Of interest, recent studies pointed out the role of ethanol itself as a potential cardioprotective agent, but a clear epidemiological evidence is still missing. The aim of this narrative review is to update current knowledge on the intracellular mechanism underlying the cardioprotective effects of polyphenols and ethanol. Furthermore, we summarized the results of epidemiological studies, emphasizing their methodological criticisms and the need for randomized clinical trials able to clarify the potential role of red wine consumption in reducing CV risk.
Conclusion: Caution in avowing underestimation of the global burden of alcohol-related diseases was particularly used.
Keywords: Alcohol, ethanol, flavonoids, polyphenols, red wine, resveratrol.
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[1] 
Renaud, S.; de Lorgeril, M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet,  1992, 339(8808), 1523-1526.
[http://dx.doi.org/10.1016/0140-6736(92)91277-F] [PMID:  1351198] 
[2] 
Criqui, M.H.; Ringel, B.L. Does diet or alcohol explain the French paradox? Lancet,  1994, 344(8939-8940), 1719-1723.
[http://dx.doi.org/10.1016/S0140-6736(94)92883-5] [PMID:  7996999] 
[3] 
de Gaetano, G.; Cerletti, C. European project. FAIR CT 97 3261 Project participants. Wine and cardiovascular disease. Nutr. Metab. Cardiovasc. Dis.,  2001, 11(4)(Suppl.), 47-50.
[PMID:  11894753] 
[4] 
Dell’Agli, M.; Buscialà, A.; Bosisio, E. Vascular effects of wine polyphenols. Cardiovasc. Res.,  2004, 63(4), 593-602.
[http://dx.doi.org/10.1016/j.cardiores.2004.03.019] [PMID:  15306214] 
[5] 
Shen, J.; Wilmot, K.A.; Ghasemzadeh, N.; Molloy, D.L.; Burkman, G.; Mekonnen, G.; Gongora, M.C.; Quyyumi, A.A.; Sperling, L.S. mediterranean dietary patterns and cardiovascular health. Annu. Rev. Nutr.,  2015, 35, 425-449.
[http://dx.doi.org/10.1146/annurev-nutr-011215-025104] [PMID:  25974696] 
[6] 
Reiner, Z.; Catapano, A.L.; De Backer, G.; Graham, I.; Taskinen, M.R.; Wiklund, O.; Agewall, S.; Alegria, E.; Chapman, M.J.; Durrington, P.; Erdine, S.; Halcox, J.; Hobbs, R.; Kjekshus, J.; Filardi, P.P.; Riccardi, G.; Storey, R.F.; Wood, D. European Association for Cardiovascular Prevention & Rehabilitation; ESC Committee for Practice Guidelines (CPG) 2008-2010 and 2010-2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur. Heart J.,  2011, 32(14), 1769-1818.
[http://dx.doi.org/10.1093/eurheartj/ehr158] [PMID:  21712404] 
[7] 
Perk, J.; De Backer, G.; Gohlke, H.; Graham, I.; Reiner, Z.; Verschuren, M.; Albus, C.; Benlian, P.; Boysen, G.; Cifkova, R.; Deaton, C.; Ebrahim, S.; Fisher, M.; Germano, G.; Hobbs, R.; Hoes, A.; Karadeniz, S.; Mezzani, A.; Prescott, E.; Ryden, L.; Scherer, M.; Syvänne, M. Scholte op Reimer, W.J.; Vrints, C.; Wood, D.; Zamorano, J.L.; Zannad, F. European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur. Heart J.,  2012, 33(13), 1635-1701.
[http://dx.doi.org/10.1093/eurheartj/ehs092] [PMID:  22555213] 
[8] 
WHO Global Status Report on Alcohol and Health 2014.Available at:. http://www.who.int/substance_abuse/publications/global_alcohol_report/en/ [Accessed date: 18 July, 2016
[9] 
Wu, X.; Beecher, G.R.; Holden, J.M.; Haytowitz, D.B.; Gebhardt, S.E.; Prior, R.L. Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. J. Agric. Food Chem.,  2006, 54(11), 4069-4075.
[http://dx.doi.org/10.1021/jf060300l] [PMID:  16719536] 
[10] 
Lin, J.; Rexrode, K.M.; Hu, F.; Albert, C.M.; Chae, C.U.; Rimm, E.B.; Stampfer, M.J.; Manson, J.E. Dietary intakes of flavonols and flavones and coronary heart disease in US women. Am. J. Epidemiol.,  2007, 165(11), 1305-1313.
[http://dx.doi.org/10.1093/aje/kwm016] [PMID:  17379619] 
[11] 
Manach, C.; Scalbert, A.; Morand, C.; Rémésy, C.; Jiménez, L. Polyphenols: food sources and bioavailability. Am. J. Clin. Nutr.,  2004, 79(5), 727-747.
[http://dx.doi.org/10.1093/ajcn/79.5.727] [PMID:  15113710] 
[12] 
Duthie, G.G.; Pedersen, M.W.; Gardner, P.T.; Morrice, P.C.; Jenkinson, A.M.; McPhail, D.B.; Steele, G.M. The effect of whisky and wine consumption on total phenol content and antioxidant capacity of plasma from healthy volunteers. Eur. J. Clin. Nutr.,  1998, 52(10), 733-736.
[http://dx.doi.org/10.1038/sj.ejcn.1600635] [PMID:  9805220] 
[13] 
Hollman, P.C.; Katan, M.B. Absorption, metabolism and health effects of dietary flavonoids in man. Biomed. Pharmacother.,  1997, 51(8), 305-310.
[http://dx.doi.org/10.1016/S0753-3322(97)88045-6] [PMID:  9436520] 
[14] 
Bell, J.R.; Donovan, J.L.; Wong, R.; Waterhouse, A.L.; German, J.B.; Walzem, R.L.; Kasim-Karakas, S.E. (+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine. Am. J. Clin. Nutr.,  2000, 71(1), 103-108.
[http://dx.doi.org/10.1093/ajcn/71.1.103] [PMID:  10617953] 
[15] 
D’Archivio, M.; Filesi, C.; Di Benedetto, R.; Gargiulo, R.; Giovannini, C.; Masella, R. Polyphenols, dietary sources and bioavailability. Ann. Ist. Super. Sanita,  2007, 43(4), 348-361.
[PMID:  18209268] 
[16] 
Day, A.J.; Williamson, G. Biomarkers for exposure to dietary flavonoids: a review of the current evidence for identification of quercetin glycosides in plasma. Br. J. Nutr.,  2001, 86(Suppl. 1), S105-S110.
[http://dx.doi.org/10.1079/BJN2001342] [PMID:  11520427] 
[17] 
Notas, G.; Nifli, A.P.; Kampa, M.; Pelekanou, V.; Alexaki, V.I.; Theodoropoulos, P.; Vercauteren, J.; Castanas, E. Quercetin accumulates in nuclear structures and triggers specific gene expression in epithelial cells. J. Nutr. Biochem.,  2012, 23(6), 656-666.
[http://dx.doi.org/10.1016/j.jnutbio.2011.03.010] [PMID:  21782406] 
[18] 
Kaindl, U.; Eyberg, I.; Rohr-Udilova, N.; Heinzle, C.; Marian, B. The dietary antioxidants resveratrol and quercetin protect cells from exogenous pro-oxidative damage. Food Chem. Toxicol.,  2008, 46(4), 1320-1326.
[http://dx.doi.org/10.1016/j.fct.2007.09.002] [PMID:  17936464] 
[19] 
Gorelik, S.; Ligumsky, M.; Kohen, R.; Kanner, J. A novel function of red wine polyphenols in humans: prevention of absorption of cytotoxic lipid peroxidation products. FASEB J.,  2008, 22(1), 41-46.
[http://dx.doi.org/10.1096/fj.07-9041com] [PMID:  17712060] 
[20] 
Boban, M.; Modun, D. Uric acid and antioxidant effects of wine. Croat. Med. J.,  2010, 51(1), 16-22.
[http://dx.doi.org/10.3325/cmj.2010.51.16] [PMID:  20162741] 
[21] 
Lu, J.; Wu, D.M.; Zheng, Y.L.; Hu, B.; Zhang, Z.F.; Shan, Q.; Zheng, Z.H.; Liu, C.M.; Wang, Y.J. Quercetin activates AMP-activated protein kinase by reducing PP2C expression protecting old mouse brain against high cholesterol-induced neurotoxicity. J. Pathol.,  2010, 222(2), 199-212.
[http://dx.doi.org/10.1002/path.2754] [PMID:  20690163] 
[22] 
Ahn, J.; Lee, H.; Kim, S.; Park, J.; Ha, T. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem. Biophys. Res. Commun.,  2008, 373(4), 545-549.
[http://dx.doi.org/10.1016/j.bbrc.2008.06.077] [PMID:  18586010] 
[23] 
Eseberri, I.; Miranda, J.; Lasa, A.; Churruca, I.; Portillo, M.P. Doses of quercetin in the range of serum concentrations exert delipidating effects in 3T3-L1 preadipocytes by acting on different stages of adipogenesis, but not in mature adipocytes. Oxid. Med. Cell. Longev., 2015.2015480943
[http://dx.doi.org/10.1155/2015/480943] [PMID:  26180590] 
[24] 
Davis, J.M.; Murphy, E.A.; Carmichael, M.D.; Davis, B. Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am. J. Physiol. Regul. Integr. Comp. Physiol.,  2009, 296(4), R1071-R1077.
[http://dx.doi.org/10.1152/ajpregu.90925.2008] [PMID:  19211721] 
[25] 
Nieman, D.C.; Williams, A.S.; Shanely, R.A.; Jin, F.; McAnulty, S.R.; Triplett, N.T.; Austin, M.D.; Henson, D.A. Quercetin’s influence on exercise performance and muscle mitochondrial biogenesis. Med. Sci. Sports Exerc.,  2010, 42(2), 338-345.
[http://dx.doi.org/10.1249/MSS.0b013e3181b18fa3] [PMID:  19927026] 
[26] 
Hung, C.H.; Chan, S.H.; Chu, P.M.; Tsai, K.L. Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation. Mol. Nutr. Food Res.,  2015, 59(10), 1905-1917.
[http://dx.doi.org/10.1002/mnfr.201500144] [PMID:  26202455] 
[27] 
Dong, J.; Zhang, X.; Zhang, L.; Bian, H.X.; Xu, N.; Bao, B.; Liu, J. Quercetin reduces obesity-associated ATM infiltration and inflammation in mice: a mechanism including AMPKα1/SIRT1. J. Lipid Res.,  2014, 55(3), 363-374.
[http://dx.doi.org/10.1194/jlr.M038786] [PMID:  24465016] 
[28] 
Virgili, F.; Acconcia, F.; Ambra, R.; Rinna, A.; Totta, P.; Marino, M. Nutritional flavonoids modulate estrogen receptor alpha signaling. IUBMB Life,  2004, 56(3), 145-151.
[http://dx.doi.org/10.1080/15216540410001685083] [PMID:  15185748] 
[29] 
Anter, E.; Chen, K.; Shapira, O.M.; Karas, R.H.; Keaney, J.F., Jr p38 mitogen-activated protein kinase activates eNOS in endothelial cells by an estrogen receptor alpha-dependent pathway in response to black tea polyphenols. Circ. Res.,  2005, 96(10), 1072-1078.
[http://dx.doi.org/10.1161/01.RES.0000168807.63013.56] [PMID:  15879307] 
[30] 
Chalopin, M.; Tesse, A.; Martínez, M.C.; Rognan, D.; Arnal, J.F.; Andriantsitohaina, R. Estrogen receptor alpha as a key target of red wine polyphenols action on the endothelium. PLoS One,  2010, 5(1)e8554
[http://dx.doi.org/10.1371/journal.pone.0008554] [PMID:  20049322] 
[31] 
Simoncini, T.; Lenzi, E.; Zöchling, A.; Gopal, S.; Goglia, L.; Russo, E.; Polak, K.; Casarosa, E.; Jungbauer, A.; Genazzani, A.D.; Genazzani, A.R. Estrogen-like effects of wine extracts on nitric oxide synthesis in human endothelial cells. Maturitas,  2011, 70(2), 169-175.
[http://dx.doi.org/10.1016/j.maturitas.2011.07.004] [PMID:  21839593] 
[32] 
Kane, M.O.; Anselm, E.; Rattmann, Y.D.; Auger, C.; Schini-Kerth, V.B. Role of gender and estrogen receptors in the rat aorta endothelium-dependent relaxation to red wine polyphenols. Vascul. Pharmacol.,  2009, 51(2-3), 140-146.
[http://dx.doi.org/10.1016/j.vph.2009.05.002] [PMID:  19520189] 
[33] 
Chalopin, M.; Soleti, R.; Benameur, T.; Tesse, A.; Faure, S.; Martínez, M.C.; Andriantsitohaina, R. Red wine polyphenol compounds favor neovascularisation through estrogen receptor α-independent mechanism in mice. PLoS One,  2014, 9(10)e110080
[http://dx.doi.org/10.1371/journal.pone.0110080] [PMID:  25299185] 
[34] 
Duarte, J.; Andriambeloson, E.; Diebolt, M.; Andriantsitohaina, R. Wine polyphenols stimulate superoxide anion production to promote calcium signaling and endothelial-dependent vasodilatation. Physiol. Res.,  2004, 53(6), 595-602.
[PMID:  15588126] 
[35] 
Andriambeloson, E.; Kleschyov, A.L.; Muller, B.; Beretz, A.; Stoclet, J.C.; Andriantsitohaina, R. Nitric oxide production and endothelium-dependent vasorelaxation induced by wine polyphenols in rat aorta. Br. J. Pharmacol.,  1997, 120(6), 1053-1058.
[http://dx.doi.org/10.1038/sj.bjp.0701011] [PMID:  9134217] 
[36] 
de Moura, R.S.; Miranda, D.Z.; Pinto, A.C.; Sicca, R.F.; Souza, M.A.; Rubenich, L.M.; Carvalho, L.C.; Rangel, B.M.; Tano, T.; Madeira, S.V.; Resende, A.C. Mechanism of the endothelium-dependent vasodilation and the antihypertensive effect of Brazilian red wine. J. Cardiovasc. Pharmacol.,  2004, 44(3), 302-309.
[http://dx.doi.org/10.1097/01.fjc.0000133060.10597.3c] [PMID:  15475826] 
[37] 
Ndiaye, M.; Chataigneau, M.; Lobysheva, I.; Chataigneau, T.; Schini-Kerth, V.B. Red wine polyphenol-induced, endothelium-dependent NO-mediated relaxation is due to the redox-sensitive PI3-kinase/Akt-dependent phosphorylation of endothelial NO-synthase in the isolated porcine coronary artery. FASEB J.,  2005, 19(3), 455-457.
[http://dx.doi.org/10.1096/fj.04-2146fje] [PMID:  15623569] 
[38] 
Anselm, E.; Chataigneau, M.; Ndiaye, M.; Chataigneau, T.; Schini-Kerth, V.B. Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS. Cardiovasc. Res.,  2007, 73(2), 404-413.
[http://dx.doi.org/10.1016/j.cardiores.2006.08.004] [PMID:  16962569] 
[39] 
Sarr, M.; Chataigneau, M.; Martins, S.; Schott, C.; El Bedoui, J.; Oak, M.H.; Muller, B.; Chataigneau, T.; Schini-Kerth, V.B. Red wine polyphenols prevent angiotensin II-induced hypertension and endothelial dysfunction in rats: role of NADPH oxidase. Cardiovasc. Res.,  2006, 71(4), 794-802.
[http://dx.doi.org/10.1016/j.cardiores.2006.05.022] [PMID:  16822492] 
[40] 
Bernátová, I.; Pechánová, O.; Babál, P.; Kyselá, S.; Stvrtina, S.; Andriantsitohaina, R. Wine polyphenols improve cardiovascular remodeling and vascular function in NO-deficient hypertension. Am. J. Physiol. Heart Circ. Physiol.,  2002, 282(3), H942-H948.
[http://dx.doi.org/10.1152/ajpheart.00724.2001] [PMID:  11834490] 
[41] 
Peng, N.; Clark, J.T.; Prasain, J.; Kim, H.; White, C.R.; Wyss, J.M. Antihypertensive and cognitive effects of grape polyphenols in estrogen-depleted, female, spontaneously hypertensive rats. Am. J. Physiol. Regul. Integr. Comp. Physiol.,  2005, 289(3), R771-R775.
[http://dx.doi.org/10.1152/ajpregu.00147.2005] [PMID:  16105821] 
[42] 
Jiménez, R.; López-Sepúlveda, R.; Kadmiri, M.; Romero, M.; Vera, R.; Sánchez, M.; Vargas, F.; O’Valle, F.; Zarzuelo, A.; Dueñas, M.; Santos-Buelga, C.; Duarte, J. Polyphenols restore endothelial function in DOCA-salt hypertension: role of endothelin-1 and NADPH oxidase. Free Radic. Biol. Med.,  2007, 43(3), 462-473.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.05.007] [PMID:  17602962] 
[43] 
Auger, C.; Gérain, P.; Laurent-Bichon, F.; Portet, K.; Bornet, A.; Caporiccio, B.; Cros, G.; Teissédre, P.L.; Rouanet, J.M. Phenolics from commercialized grape extracts prevent early atherosclerotic lesions in hamsters by mechanisms other than antioxidant effect. J. Agric. Food Chem.,  2004, 52(16), 5297-5302.
[http://dx.doi.org/10.1021/jf040125d] [PMID:  15291511] 
[44] 
Shanmuganayagam, D.; Warner, T.F.; Krueger, C.G.; Reed, J.D.; Folts, J.D. Concord grape juice attenuates platelet aggregation, serum cholesterol and development of atheroma in hypercholesterolemic rabbits. Atherosclerosis,  2007, 190(1), 135-142.
[http://dx.doi.org/10.1016/j.atherosclerosis.2006.03.017] [PMID:  16780846] 
[45] 
Pignatelli, P.; Pulcinelli, F.M.; Celestini, A.; Lenti, L.; Ghiselli, A.; Gazzaniga, P.P.; Violi, F. The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide. Am. J. Clin. Nutr.,  2000, 72(5), 1150-1155.
[http://dx.doi.org/10.1093/ajcn/72.5.1150] [PMID:  11063442] 
[46] 
Freedman, J.E.; Parker, C., III; Li, L.; Perlman, J.A.; Frei, B.; Ivanov, V.; Deak, L.R.; Iafrati, M.D.; Folts, J.D. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation,  2001, 103(23), 2792-2798.
[http://dx.doi.org/10.1161/01.CIR.103.23.2792] [PMID:  11401934] 
[47] 
Al-Awwadi, N.A.; Araiz, C.; Bornet, A.; Delbosc, S.; Cristol, J.P.; Linck, N.; Azay, J.; Teissedre, P.L.; Cros, G. Extracts enriched in different polyphenolic families normalize increased cardiac NADPH oxidase expression while having differential effects on insulin resistance, hypertension, and cardiac hypertrophy in high-fructose-fed rats. J. Agric. Food Chem.,  2005, 53(1), 151-157.
[http://dx.doi.org/10.1021/jf048919f] [PMID:  15631522] 
[48] 
Ihm, S.H.; Lee, J.O.; Kim, S.J.; Seung, K.B.; Schini-Kerth, V.B.; Chang, K.; Oak, M.H. Catechin prevents endothelial dysfunction in the prediabetic stage of OLETF rats by reducing vascular NADPH oxidase activity and expression. Atherosclerosis,  2009, 206(1), 47-53.
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.01.036] [PMID:  19264308] 
[49] 
Agouni, A.; Lagrue-Lak-Hal, A.H.; Mostefai, H.A.; Tesse, A.; Mulder, P.; Rouet, P.; Desmoulin, F.; Heymes, C.; Martínez, M.C.; Andriantsitohaina, R. Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa). PLoS One,  2009, 4(5)e5557
[http://dx.doi.org/10.1371/journal.pone.0005557] [PMID:  19440378] 
[50] 
Terra, X.; Montagut, G.; Bustos, M.; Llopiz, N.; Ardèvol, A.; Bladé, C.; Fernández-Larrea, J.; Pujadas, G.; Salvadó, J.; Arola, L.; Blay, M. Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J. Nutr. Biochem.,  2009, 20(3), 210-218.
[http://dx.doi.org/10.1016/j.jnutbio.2008.02.005] [PMID:  18602813] 
[51] 
Rangel-Huerta, O.D.; Pastor-Villaescusa, B.; Aguilera, C.M.; Gil, A. A systematic review of the efficacy of bioactive compounds in cardiovascular disease: phenolic compounds. Nutrients,  2015, 7(7), 5177-5216.
[http://dx.doi.org/10.3390/nu7075177] [PMID:  26132993] 
[52] 
Agewall, S.; Wright, S.; Doughty, R.N.; Whalley, G.A.; Duxbury, M.; Sharpe, N. Does a glass of red wine improve endothelial function? Eur. Heart J.,  2000, 21(1), 74-78.
[http://dx.doi.org/10.1053/euhj.1999.1759] [PMID:  10610747] 
[53] 
Hashimoto, M.; Kim, S.; Eto, M.; Iijima, K.; Ako, J.; Yoshizumi, M.; Akishita, M.; Kondo, K.; Itakura, H.; Hosoda, K.; Toba, K.; Ouchi, Y. Effect of acute intake of red wine on flow-mediated vasodilatation of the brachial artery. Am J Cardiol,  2001, 8(12), 1457-1460.A1459. 
[http://dx.doi.org/10.1016/S0002-9149(01)02137-3] 
[54] 
Boban, M.; Modun, D.; Music, I.; Vukovic, J.; Brizic, I.; Salamunic, I.; Obad, A.; Palada, I.; Dujic, Z. Red wine induced modulation of vascular function: separating the role of polyphenols, ethanol, and urates. J. Cardiovasc. Pharmacol.,  2006, 47(5), 695-701.
[http://dx.doi.org/10.1097/01.fjc.0000211762.06271.ce] [PMID:  16775510] 
[55] 
Karatzi, K.; Papamichael, C.; Karatzis, E.; Papaioannou, T.G.; Voidonikola, P.T.; Vamvakou, G.D.; Lekakis, J.; Zampelas, A. Postprandial improvement of endothelial function by red wine and olive oil antioxidants: a synergistic effect of components of the Mediterranean diet. J. Am. Coll. Nutr.,  2008, 27(4), 448-453.
[http://dx.doi.org/10.1080/07315724.2008.10719724] [PMID:  18978163] 
[56] 
Engler, M.B.; Engler, M.M.; Chen, C.Y.; Malloy, M.J.; Browne, A.; Chiu, E.Y.; Kwak, H.K.; Milbury, P.; Paul, S.M.; Blumberg, J.; Mietus-Snyder, M.L. Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. J. Am. Coll. Nutr.,  2004, 23(3), 197-204.
[http://dx.doi.org/10.1080/07315724.2004.10719361] [PMID:  15190043] 
[57] 
Clifton, P.M. Effect of grape seed extract and quercetin on cardiovascular and endothelial parameters in high-risk subjects. J. Biomed. Biotechnol.,  2004, 2004(5), 272-278.
[http://dx.doi.org/10.1155/S1110724304403088] [PMID:  15577189] 
[58] 
Schroeter, H.; Heiss, C.; Balzer, J.; Kleinbongard, P.; Keen, C.L.; Hollenberg, N.K.; Sies, H.; Kwik-Uribe, C.; Schmitz, H.H.; Kelm, M. (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc. Natl. Acad. Sci. USA,  2006, 103(4), 1024-1029.
[http://dx.doi.org/10.1073/pnas.0510168103] [PMID:  16418281] 
[59] 
Hampton, S.M.; Isherwood, C.; Kirkpatrick, V.J.; Lynne-Smith, A.C.; Griffin, B.A. The influence of alcohol consumed with a meal on endothelial function in healthy individuals. J. Hum. Nutr. Diet.,  2010, 23(2), 120-125.
[http://dx.doi.org/10.1111/j.1365-277X.2009.01021.x] [PMID:  20113387] 
[60] 
Hall, W.L.; Formanuik, N.L.; Harnpanich, D.; Cheung, M.; Talbot, D.; Chowienczyk, P.J.; Sanders, T.A. A meal enriched with soy isoflavones increases nitric oxide-mediated vasodilation in healthy postmenopausal women. J. Nutr.,  2008, 138(7), 1288-1292.
[http://dx.doi.org/10.1093/jn/138.7.1288] [PMID:  18567749] 
[61] 
Papamichael, C.; Karatzis, E.; Karatzi, K.; Aznaouridis, K.; Papaioannou, T.; Protogerou, A.; Stamatelopoulos, K.; Zampelas, A.; Lekakis, J.; Mavrikakis, M. Red wine’s antioxidants counteract acute endothelial dysfunction caused by cigarette smoking in healthy nonsmokers. Am. Heart J.,  2004, 147(2)E5
[http://dx.doi.org/10.1016/S0002-8703(03)00468-X] [PMID:  14760339] 
[62] 
Heiss, C.; Kleinbongard, P.; Dejam, A.; Perré, S.; Schroeter, H.; Sies, H.; Kelm, M. Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. J. Am. Coll. Cardiol.,  2005, 46(7), 1276-1283.
[http://dx.doi.org/10.1016/j.jacc.2005.06.055] [PMID:  16198843] 
[63] 
Papamichael, C.; Karatzi, K.; Karatzis, E.; Papaioannou, T.G.; Katsichti, P.; Zampelas, A.; Lekakis, J. Combined acute effects of red wine consumption and cigarette smoking on haemodynamics of young smokers. J. Hypertens.,  2006, 24(7), 1287-1292.
[http://dx.doi.org/10.1097/01.hjh.0000234108.08368.01] [PMID:  16794477] 
[64] 
Coimbra, S.R.; Lage, S.H.; Brandizzi, L.; Yoshida, V.; da Luz, P.L. The action of red wine and purple grape juice on vascular reactivity is independent of plasma lipids in hypercholesterolemic patients. Braz. J. Med. Biol. Res.,  2005, 38(9), 1339-1347.
[http://dx.doi.org/10.1590/S0100-879X2005000900008] [PMID:  16138217] 
[65] 
Faridi, Z.; Njike, V.Y.; Dutta, S.; Ali, A.; Katz, D.L. Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial. Am. J. Clin. Nutr.,  2008, 88(1), 58-63.
[http://dx.doi.org/10.1093/ajcn/88.1.58] [PMID:  18614724] 
[66] 
Balzer, J.; Rassaf, T.; Heiss, C.; Kleinbongard, P.; Lauer, T.; Merx, M.; Heussen, N.; Gross, H.B.; Keen, C.L.; Schroeter, H.; Kelm, M. Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial. J. Am. Coll. Cardiol.,  2008, 51(22), 2141-2149.
[http://dx.doi.org/10.1016/j.jacc.2008.01.059] [PMID:  18510961] 
[67] 
Berry, N.M.; Davison, K.; Coates, A.M.; Buckley, J.D.; Howe, P.R. Impact of cocoa flavanol consumption on blood pressure responsiveness to exercise. Br. J. Nutr.,  2010, 103(10), 1480-1484.
[http://dx.doi.org/10.1017/S0007114509993382] [PMID:  20082737] 
[68] 
Aviram, M.; Dornfeld, L. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis,  2001, 158(1), 195-198.
[http://dx.doi.org/10.1016/S0021-9150(01)00412-9] [PMID:  11500191] 
[69] 
Taubert, D.; Berkels, R.; Roesen, R.; Klaus, W. Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA,  2003, 290(8), 1029-1030.
[http://dx.doi.org/10.1001/jama.290.8.1029] [PMID:  12941673] 
[70] 
Park, Y.K.; Kim, J.S.; Kang, M.H. Concord grape juice supplementation reduces blood pressure in Korean hypertensive men: double-blind, placebo controlled intervention trial. Biofactors,  2004, 22(1-4), 145-147.
[http://dx.doi.org/10.1002/biof.5520220128] [PMID:  15630270] 
[71] 
Dohadwala, M.M.; Hamburg, N.M.; Holbrook, M.; Kim, B.H.; Duess, M.A.; Levit, A.; Titas, M.; Chung, W.B.; Vincent, F.B.; Caiano, T.L.; Frame, A.A.; Keaney, J.F., Jr; Vita, J.A. Effects of Concord grape juice on ambulatory blood pressure in prehypertension and stage 1 hypertension. Am. J. Clin. Nutr.,  2010, 92(5), 1052-1059.
[http://dx.doi.org/10.3945/ajcn.2010.29905] [PMID:  20844075] 
[72] 
Stein, J.H.; Keevil, J.G.; Wiebe, D.A.; Aeschlimann, S.; Folts, J.D. Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation,  1999, 100(10), 1050-1055.
[http://dx.doi.org/10.1161/01.CIR.100.10.1050] [PMID:  10477529] 
[73] 
Aviram, M.; Rosenblat, M.; Gaitini, D.; Nitecki, S.; Hoffman, A.; Dornfeld, L.; Volkova, N.; Presser, D.; Attias, J.; Liker, H.; Hayek, T. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin. Nutr.,  2004, 23(3), 423-433.
[http://dx.doi.org/10.1016/j.clnu.2003.10.002] [PMID:  15158307] 
[74] 
Karatzi, K.; Papamichael, C.; Aznaouridis, K.; Karatzis, E.; Lekakis, J.; Matsouka, C.; Boskou, G.; Chiou, A.; Sitara, M.; Feliou, G.; Kontoyiannis, D.; Zampelas, A.; Mavrikakis, M. Constituents of red wine other than alcohol improve endothelial function in patients with coronary artery disease. Coron. Artery Dis.,  2004, 15(8), 485-490.
[http://dx.doi.org/10.1097/00019501-200412000-00005] [PMID:  15585989] 
[75] 
Widlansky, M.E.; Hamburg, N.M.; Anter, E.; Holbrook, M.; Kahn, D.F.; Elliott, J.G.; Keaney, J.F., Jr; Vita, J.A. Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease. J. Am. Coll. Nutr.,  2007, 26(2), 95-102.
[http://dx.doi.org/10.1080/07315724.2007.10719590] [PMID:  17536120] 
[76] 
Chou, E.J.; Keevil, J.G.; Aeschlimann, S.; Wiebe, D.A.; Folts, J.D.; Stein, J.H. Effect of ingestion of purple grape juice on endothelial function in patients with coronary heart disease. Am. J. Cardiol.,  2001, 88(5), 553-555.
[http://dx.doi.org/10.1016/S0002-9149(01)01738-6] [PMID:  11524068] 
[77] 
Duffy, S.J.; Keaney, J.F., Jr; Holbrook, M.; Gokce, N.; Swerdloff, P.L.; Frei, B.; Vita, J.A. Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation,  2001, 104(2), 151-156.
[http://dx.doi.org/10.1161/01.CIR.104.2.151] [PMID:  11447078] 
[78] 
Burns, J.; Yokota, T.; Ashihara, H.; Lean, M.E.; Crozier, A. Plant foods and herbal sources of resveratrol. J. Agric. Food Chem.,  2002, 50(11), 3337-3340.
[http://dx.doi.org/10.1021/jf0112973] [PMID:  12010007] 
[79] 
Das, D.K.; Maulik, N. Resveratrol in cardioprotection: a therapeutic promise of alternative medicine. Mol. Interv.,  2006, 6(1), 36-47.
[http://dx.doi.org/10.1124/mi.6.1.7] [PMID:  16507749] 
[80] 
Goswami, S.K.; Das, D.K. Resveratrol and chemoprevention. Cancer Lett.,  2009, 284(1), 1-6.
[http://dx.doi.org/10.1016/j.canlet.2009.01.041] [PMID:  19261378] 
[81] 
Goldberg, D.M.; Tsang, E.; Karumanchiri, A.; Diamandis, E.; Soleas, G.; Ng, E. Method to assay the concentrations of phenolic constituents of biological interest in wines. Anal. Chem.,  1996, 68(10), 1688-1694.
[http://dx.doi.org/10.1021/ac951083i] [PMID:  8651480] 
[82] 
Pervaiz, S. Resveratrol: from grapevines to mammalian biology. FASEB J.,  2003, 17(14), 1975-1985.
[http://dx.doi.org/10.1096/fj.03-0168rev] [PMID:  14597667] 
[83] 
Fornara, V.; Onelli, E.; Sparvoli, F.; Rossoni, M.; Aina, R.; Marino, G.; Citterio, S. Localization of stilbene synthase in Vitis vinifera L. during berry development. Protoplasma,  2008, 233(1-2), 83-93.
[http://dx.doi.org/10.1007/s00709-008-0309-8] [PMID:  18615235] 
[84] 
Wang, W.; Tang, K.; Yang, H.R.; Wen, P.F.; Zhang, P.; Wang, H.L.; Huang, W.D. Distribution of resveratrol and stilbene synthase in young grape plants (Vitis vinifera L. cv. Cabernet Sauvignon) and the effect of UV-C on its accumulation. Plant Physiol. Biochem.,  2010, 48(2-3), 142-152.
[http://dx.doi.org/10.1016/j.plaphy.2009.12.002] [PMID:  20060310] 
[85] 
Soleas, G.J.; Diamandis, E.P.; Goldberg, D.M. Resveratrol: a molecule whose time has come? And gone? Clin. Biochem.,  1997, 30(2), 91-113.
[http://dx.doi.org/10.1016/S0009-9120(96)00155-5] [PMID:  9127691] 
[86] 
Kundu, J.K.; Surh, Y.J. Cancer chemopreventive and therapeutic potential of resveratrol: mechanistic perspectives. Cancer Lett.,  2008, 269(2), 243-261.
[http://dx.doi.org/10.1016/j.canlet.2008.03.057] [PMID:  18550275] 
[87] 
Bertelli, A.A.; Giovannini, L.; Bernini, W.; Migliori, M.; Fregoni, M.; Bavaresco, L.; Bertelli, A. Antiplatelet activity of cis-resveratrol. Drugs Exp. Clin. Res.,  1996, 22(2), 61-63.
[PMID:  8998912] 
[88] 
Adrian, M.; Jeandet, P.; Veneau, J.; Weston, L.A.; Bessis, R. Biological Activity of Resveratrol, a Stilbenic Compound from Grapevines, Against Botrytis cinerea, the Causal Agent for Gray Mold. J. Chem. Ecol.,  1997, 23(7), 1689-1702.
[http://dx.doi.org/10.1023/B:JOEC.0000006444.79951.75] 
[89] 
Wong, R.H.; Howe, P.R.; Buckley, J.D.; Coates, A.M.; Kunz, I.; Berry, N.M. Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr. Metab. Cardiovasc. Dis.,  2011, 21(11), 851-856.
[http://dx.doi.org/10.1016/j.numecd.2010.03.003] [PMID:  20674311] 
[90] 
Förstermann, U.; Li, H. Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling. Br. J. Pharmacol.,  2011, 164(2), 213-223.
[http://dx.doi.org/10.1111/j.1476-5381.2010.01196.x] [PMID:  21198553] 
[91] 
Zhang, Q.J.; Wang, Z.; Chen, H.Z.; Zhou, S.; Zheng, W.; Liu, G.; Wei, Y.S.; Cai, H.; Liu, D.P.; Liang, C.C. Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovasc. Res.,  2008, 80(2), 191-199.
[http://dx.doi.org/10.1093/cvr/cvn224] [PMID:  18689793] 
[92] 
Csiszar, A.; Labinskyy, N.; Pinto, J.T.; Ballabh, P.; Zhang, H.; Losonczy, G.; Pearson, K.; de Cabo, R.; Pacher, P.; Zhang, C.; Ungvari, Z. Resveratrol induces mitochondrial biogenesis in endothelial cells. Am. J. Physiol. Heart Circ. Physiol.,  2009, 297(1), H13-H20.
[http://dx.doi.org/10.1152/ajpheart.00368.2009] [PMID:  19429820] 
[93] 
Klinge, C.M.; Blankenship, K.A.; Risinger, K.E.; Bhatnagar, S.; Noisin, E.L.; Sumanasekera, W.K.; Zhao, L.; Brey, D.M.; Keynton, R.S. Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells. J. Biol. Chem.,  2005, 280(9), 7460-7468.
[http://dx.doi.org/10.1074/jbc.M411565200] [PMID:  15615701] 
[94] 
Klinge, C.M.; Wickramasinghe, N.S.; Ivanova, M.M.; Dougherty, S.M. Resveratrol stimulates nitric oxide production by increasing estrogen receptor alpha-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells. FASEB J.,  2008, 22(7), 2185-2197.
[http://dx.doi.org/10.1096/fj.07-103366] [PMID:  18296501] 
[95] 
Mattagajasingh, I.; Kim, C.S.; Naqvi, A.; Yamamori, T.; Hoffman, T.A.; Jung, S.B.; DeRicco, J.; Kasuno, K.; Irani, K. SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc. Natl. Acad. Sci. USA,  2007, 104(37), 14855-14860.
[http://dx.doi.org/10.1073/pnas.0704329104] [PMID:  17785417] 
[96] 
Frombaum, M.; Therond, P.; Djelidi, R.; Beaudeux, J.L.; Bonnefont-Rousselot, D.; Borderie, D. Piceatannol is more effective than resveratrol in restoring endothelial cell dimethylarginine dimethylaminohydrolase expression and activity after high-glucose oxidative stress. Free Radic. Res.,  2011, 45(3), 293-302.
[http://dx.doi.org/10.3109/10715762.2010.527337] [PMID:  21235286] 
[97] 
Penumathsa, S.V.; Koneru, S.; Samuel, S.M.; Maulik, G.; Bagchi, D.; Yet, S.F.; Menon, V.P.; Maulik, N. Strategic targets to induce neovascularization by resveratrol in hypercholesterolemic rat myocardium: role of caveolin-1, endothelial nitric oxide synthase, hemeoxygenase-1, and vascular endothelial growth factor. Free Radic. Biol. Med.,  2008, 45(7), 1027-1034.
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.07.012] [PMID:  18694817] 
[98] 
Xia, N.; Daiber, A.; Habermeier, A.; Closs, E.I.; Thum, T.; Spanier, G.; Lu, Q.; Oelze, M.; Torzewski, M.; Lackner, K.J.; Münzel, T.; Förstermann, U.; Li, H. Resveratrol reverses endothelial nitric-oxide synthase uncoupling in apolipoprotein E knockout mice. J. Pharmacol. Exp. Ther.,  2010, 335(1), 149-154.
[http://dx.doi.org/10.1124/jpet.110.168724] [PMID:  20610621] 
[99] 
Li, H.; Xia, N.; Förstermann, U. Cardiovascular effects and molecular targets of resveratrol. Nitric Oxide,  2012, 26(2), 102-110.
[http://dx.doi.org/10.1016/j.niox.2011.12.006] [PMID:  22245452] 
[100] 
Howitz, K.T.; Bitterman, K.J.; Cohen, H.Y.; Lamming, D.W.; Lavu, S.; Wood, J.G.; Zipkin, R.E.; Chung, P.; Kisielewski, A.; Zhang, L.L.; Scherer, B.; Sinclair, D.A. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature,  2003, 425(6954), 191-196.
[http://dx.doi.org/10.1038/nature01960] [PMID:  12939617] 
[101] 
Beher, D.; Wu, J.; Cumine, S.; Kim, K.W.; Lu, S.C.; Atangan, L.; Wang, M. Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem. Biol. Drug Des.,  2009, 74(6), 619-624.
[http://dx.doi.org/10.1111/j.1747-0285.2009.00901.x] [PMID:  19843076] 
[102] 
Pacholec, M.; Bleasdale, J.E.; Chrunyk, B.; Cunningham, D.; Flynn, D.; Garofalo, R.S.; Griffith, D.; Griffor, M.; Loulakis, P.; Pabst, B.; Qiu, X.; Stockman, B.; Thanabal, V.; Varghese, A.; Ward, J.; Withka, J.; Ahn, K. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J. Biol. Chem.,  2010, 285(11), 8340-8351.
[http://dx.doi.org/10.1074/jbc.M109.088682] [PMID:  20061378] 
[103] 
Hu, Y.; Liu, J.; Wang, J.; Liu, Q. The controversial links among calorie restriction, SIRT1, and resveratrol. Free Radic. Biol. Med.,  2011, 51(2), 250-256.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.04.034] [PMID:  21569839] 
[104] 
Dai, H.; Kustigian, L.; Carney, D.; Case, A.; Considine, T.; Hubbard, B.P.; Perni, R.B.; Riera, T.V.; Szczepankiewicz, B.; Vlasuk, G.P.; Stein, R.L. SIRT1 activation by small molecules: kinetic and biophysical evidence for direct interaction of enzyme and activator. J. Biol. Chem.,  2010, 285(43), 32695-32703.
[http://dx.doi.org/10.1074/jbc.M110.133892] [PMID:  20702418] 
[105] 
Mukherjee, S.; Lekli, I.; Gurusamy, N.; Bertelli, A.A.; Das, D.K. Expression of the longevity proteins by both red and white wines and their cardioprotective components, resveratrol, tyrosol, and hydroxytyrosol. Free Radic. Biol. Med.,  2009, 46(5), 573-578.
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.11.005] [PMID:  19071213] 
[106] 
Cantó, C.; Gerhart-Hines, Z.; Feige, J.N.; Lagouge, M.; Noriega, L.; Milne, J.C.; Elliott, P.J.; Puigserver, P.; Auwerx, J. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature,  2009, 458(7241), 1056-1060.
[http://dx.doi.org/10.1038/nature07813] [PMID:  19262508] 
[107] 
Csiszar, A.; Smith, K.; Labinskyy, N.; Orosz, Z.; Rivera, A.; Ungvari, Z. Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells: role of NF-kappaB inhibition. Am. J. Physiol. Heart Circ. Physiol.,  2006, 291(4), H1694-H1699.
[http://dx.doi.org/10.1152/ajpheart.00340.2006] [PMID:  16973825] 
[108] 
Csiszar, A.; Labinskyy, N.; Podlutsky, A.; Kaminski, P.M.; Wolin, M.S.; Zhang, C.; Mukhopadhyay, P.; Pacher, P.; Hu, F.; de Cabo, R.; Ballabh, P.; Ungvari, Z. Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations. Am. J. Physiol. Heart Circ. Physiol.,  2008, 294(6), H2721-H2735.
[http://dx.doi.org/10.1152/ajpheart.00235.2008] [PMID:  18424637] 
[109] 
Labinskyy, N.; Csiszar, A.; Veress, G.; Stef, G.; Pacher, P.; Oroszi, G.; Wu, J.; Ungvari, Z. Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen. Curr. Med. Chem.,  2006, 13(9), 989-996.
[http://dx.doi.org/10.2174/092986706776360987] [PMID:  16611080] 
[110] 
Kundu, J.K.; Shin, Y.K.; Kim, S.H.; Surh, Y.J. Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-kappaB in mouse skin by blocking IkappaB kinase activity. Carcinogenesis,  2006, 27(7), 1465-1474.
[http://dx.doi.org/10.1093/carcin/bgi349] [PMID:  16474181] 
[111] 
Manna, S.K.; Mukhopadhyay, A.; Aggarwal, B.B. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J. Immunol.,  2000, 164(12), 6509-6519.
[http://dx.doi.org/10.4049/jimmunol.164.12.6509] [PMID:  10843709] 
[112] 
Leonard, S.S.; Xia, C.; Jiang, B.H.; Stinefelt, B.; Klandorf, H.; Harris, G.K.; Shi, X. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem. Biophys. Res. Commun.,  2003, 309(4), 1017-1026.
[http://dx.doi.org/10.1016/j.bbrc.2003.08.105] [PMID:  13679076] 
[113] 
Ungvari, Z.; Orosz, Z.; Rivera, A.; Labinskyy, N.; Xiangmin, Z.; Olson, S.; Podlutsky, A.; Csiszar, A. Resveratrol increases vascular oxidative stress resistance. Am. J. Physiol. Heart Circ. Physiol.,  2007, 292(5), H2417-H2424.
[http://dx.doi.org/10.1152/ajpheart.01258.2006] [PMID:  17220179] 
[114] 
Li, Y.; Cao, Z.; Zhu, H. Upregulation of endogenous antioxidants and phase 2 enzymes by the red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stress. Pharmacol. Res.,  2006, 53(1), 6-15.
[http://dx.doi.org/10.1016/j.phrs.2005.08.002] [PMID:  16169743] 
[115] 
Spanier, G.; Xu, H.; Xia, N.; Tobias, S.; Deng, S.; Wojnowski, L.; Forstermann, U.; Li, H. Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4). J. Physiol. Pharmacol.,  2009, 60(Suppl. 4), 111-116.
[PMID:  20083859] 
[116] 
Tanno, M.; Kuno, A.; Yano, T.; Miura, T.; Hisahara, S.; Ishikawa, S.; Shimamoto, K.; Horio, Y. Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure. J. Biol. Chem.,  2010, 285(11), 8375-8382.
[http://dx.doi.org/10.1074/jbc.M109.090266] [PMID:  20089851] 
[117] 
Kaga, S.; Zhan, L.; Matsumoto, M.; Maulik, N. Resveratrol enhances neovascularization in the infarcted rat myocardium through the induction of thioredoxin-1, heme oxygenase-1 and vascular endothelial growth factor. J. Mol. Cell. Cardiol.,  2005, 39(5), 813-822.
[http://dx.doi.org/10.1016/j.yjmcc.2005.08.003] [PMID:  16198371] 
[118] 
Juan, S.H.; Cheng, T.H.; Lin, H.C.; Chu, Y.L.; Lee, W.S. Mechanism of concentration-dependent induction of heme oxygenase-1 by resveratrol in human aortic smooth muscle cells. Biochem. Pharmacol.,  2005, 69(1), 41-48.
[http://dx.doi.org/10.1016/j.bcp.2004.09.015] [PMID:  15588712] 
[119] 
Dudley, J.; Das, S.; Mukherjee, S.; Das, D.K. Resveratrol, a unique phytoalexin present in red wine, delivers either survival signal or death signal to the ischemic myocardium depending on dose. J. Nutr. Biochem.,  2009, 20(6), 443-452.
[http://dx.doi.org/10.1016/j.jnutbio.2008.05.003] [PMID:  18789672] 
[120] 
Ungvari, Z.; Orosz, Z.; Labinskyy, N.; Rivera, A.; Xiangmin, Z.; Smith, K.; Csiszar, A. Increased mitochondrial H2O2 production promotes endothelial NF-kappaB activation in aged rat arteries. Am. J. Physiol. Heart Circ. Physiol.,  2007, 293(1), H37-H47.
[http://dx.doi.org/10.1152/ajpheart.01346.2006] [PMID:  17416599] 
[121] 
Yu, H.P.; Hwang, T.L.; Hwang, T.L.; Yen, C.H.; Lau, Y.T. Resveratrol prevents endothelial dysfunction and aortic superoxide production after trauma hemorrhage through estrogen receptor-dependent hemeoxygenase-1 pathway. Crit. Care Med.,  2010, 38(4), 1147-1154.
[http://dx.doi.org/10.1097/CCM.0b013e3181cd124e] [PMID:  20081535] 
[122] 
Chow, S.E.; Hshu, Y.C.; Wang, J.S.; Chen, J.K. Resveratrol
attenuates oxLDL-stimulated NADPH oxidase activity and
protects endothelial cells from oxidative functional damages J Appl Physiol (1985) ,  2007, 102(4), 1520-1527.
[123] 
Shen, M.Y.; Hsiao, G.; Liu, C.L.; Fong, T.H.; Lin, K.H.; Chou, D.S.; Sheu, J.R. Inhibitory mechanisms of resveratrol in platelet activation: pivotal roles of p38 MAPK and NO/cyclic GMP. Br. J. Haematol.,  2007, 139(3), 475-485.
[http://dx.doi.org/10.1111/j.1365-2141.2007.06788.x] [PMID:  17868048] 
[124] 
Zordoky, B.N.; Robertson, I.M.; Dyck, J.R. Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases. Biochim. Biophys. Acta,  2015, 1852(6), 1155-1177.
[http://dx.doi.org/10.1016/j.bbadis.2014.10.016] [PMID:  25451966] 
[125] 
Rivera, L.; Morón, R.; Zarzuelo, A.; Galisteo, M. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem. Pharmacol.,  2009, 77(6), 1053-1063.
[http://dx.doi.org/10.1016/j.bcp.2008.11.027] [PMID:  19100718] 
[126] 
Dolinsky, V.W.; Chakrabarti, S.; Pereira, T.J.; Oka, T.; Levasseur, J.; Beker, D.; Zordoky, B.N.; Morton, J.S.; Nagendran, J.; Lopaschuk, G.D.; Davidge, S.T.; Dyck, J.R. Resveratrol prevents hypertension and cardiac hypertrophy in hypertensive rats and mice. Biochim. Biophys. Acta,  2013, 1832(10), 1723-1733.
[http://dx.doi.org/10.1016/j.bbadis.2013.05.018] [PMID:  23707558] 
[127] 
Liu, Z.; Song, Y.; Zhang, X.; Liu, Z.; Zhang, W.; Mao, W.; Wang, W.; Cui, W.; Zhang, X.; Jia, X.; Li, N.; Han, C.; Liu, C. Effects of trans-resveratrol on hypertension-induced cardiac hypertrophy using the partially nephrectomized rat model. Clin. Exp. Pharmacol. Physiol.,  2005, 32(12), 1049-1054.
[http://dx.doi.org/10.1111/j.1440-1681.2005.04299.x] [PMID:  16445570] 
[128] 
Chan, V.; Fenning, A.; Iyer, A.; Hoey, A.; Brown, L. Resveratrol improves cardiovascular function in DOCA-salt hypertensive rats. Curr. Pharm. Biotechnol.,  2011, 12(3), 429-436.
[http://dx.doi.org/10.2174/138920111794480552] [PMID:  20874677] 
[129] 
Rimbaud, S.; Ruiz, M.; Piquereau, J.; Mateo, P.; Fortin, D.; Veksler, V.; Garnier, A.; Ventura-Clapier, R. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure. PLoS One,  2011, 6(10)e26391
[http://dx.doi.org/10.1371/journal.pone.0026391] [PMID:  22028869] 
[130] 
Liu, Y.; Ma, W.; Zhang, P.; He, S.; Huang, D. Effect of resveratrol on blood pressure: a meta-analysis of randomized controlled trials. Clin. Nutr.,  2015, 34(1), 27-34.
[http://dx.doi.org/10.1016/j.clnu.2014.03.009] [PMID:  24731650] 
[131] 
Cao, X.; Luo, T.; Luo, X.; Tang, Z. Resveratrol prevents AngII-induced hypertension via AMPK activation and RhoA/ROCK suppression in mice. Hypertens. Res.,  2014, 37(9), 803-810.
[http://dx.doi.org/10.1038/hr.2014.90] [PMID:  24965170] 
[132] 
Wang, Z.; Zou, J.; Cao, K.; Hsieh, T.C.; Huang, Y.; Wu, J.M. Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels. Int. J. Mol. Med.,  2005, 16(4), 533-540.
[PMID:  16142383] 
[133] 
Göçmen, A.Y.; Burgucu, D.; Gümüşlü, S. Effect of resveratrol on platelet activation in hypercholesterolemic rats: CD40-CD40L system as a potential target. Appl. Physiol. Nutr. Metab.,  2011, 36(3), 323-330.
[http://dx.doi.org/10.1139/h11-022] [PMID:  21574786] 
[134] 
Yashiro, T.; Nanmoku, M.; Shimizu, M.; Inoue, J.; Sato, R. Resveratrol increases the expression and activity of the low density lipoprotein receptor in hepatocytes by the proteolytic activation of the sterol regulatory element-binding proteins. Atherosclerosis,  2012, 220(2), 369-374.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.11.006] [PMID:  22153697] 
[135] 
Sahebkar, A. Effects of resveratrol supplementation on plasma lipids: a systematic review and meta-analysis of randomized controlled trials. Nutr. Rev.,  2013, 71(12), 822-835.
[http://dx.doi.org/10.1111/nure.12081] [PMID:  24111838] 
[136] 
Bhatt, J.K.; Thomas, S.; Nanjan, M.J. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr. Res.,  2012, 32(7), 537-541.
[http://dx.doi.org/10.1016/j.nutres.2012.06.003] [PMID:  22901562] 
[137] 
Timmers, S.; Konings, E.; Bilet, L.; Houtkooper, R.H.; van de Weijer, T.; Goossens, G.H.; Hoeks, J.; van der Krieken, S.; Ryu, D.; Kersten, S.; Moonen-Kornips, E.; Hesselink, M.K.C.; Kunz, I.; Schrauwen-Hinderling, V.B.; Blaak, E.; Auwerx, J.; Schrauwen, P. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab.,  2011, 14(5), 612-622.
[http://dx.doi.org/10.1016/j.cmet.2011.10.002] [PMID:  22055504] 
[138] 
Tomé-Carneiro, J.; Gonzálvez, M.; Larrosa, M.; García-Almagro, F.J.; Avilés-Plaza, F.; Parra, S.; Yáñez-Gascón, M.J.; Ruiz-Ros, J.A.; García-Conesa, M.T.; Tomás-Barberán, F.A.; Espín, J.C. Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: a triple-blind, 6-month follow-up, placebo-controlled, randomized trial. Mol. Nutr. Food Res.,  2012, 56(5), 810-821.
[http://dx.doi.org/10.1002/mnfr.201100673] [PMID:  22648627] 
[139] 
Khandelwal, A.R.; Hebert, V.Y.; Dugas, T.R. Essential role of ER-alpha-dependent NO production in resveratrol-mediated inhibition of restenosis. Am. J. Physiol. Heart Circ. Physiol.,  2010, 299(5), H1451-H1458.
[http://dx.doi.org/10.1152/ajpheart.00369.2010] [PMID:  20709862] 
[140] 
Belguendouz, L.; Fremont, L.; Linard, A. Resveratrol inhibits metal ion-dependent and independent peroxidation of porcine low-density lipoproteins. Biochem. Pharmacol.,  1997, 53(9), 1347-1355.
[http://dx.doi.org/10.1016/S0006-2952(96)00820-9] [PMID:  9214696] 
[141] 
Kim, J.W.; Lim, S.C.; Lee, M.Y.; Lee, J.W.; Oh, W.K.; Kim, S.K.; Kang, K.W. Inhibition of neointimal formation by trans-resveratrol: role of phosphatidyl inositol 3-kinase-dependent Nrf2 activation in heme oxygenase-1 induction. Mol. Nutr. Food Res.,  2010, 54(10), 1497-1505.
[http://dx.doi.org/10.1002/mnfr.201000016] [PMID:  20486211] 
[142] 
Brito, P.M.; Devillard, R.; Nègre-Salvayre, A.; Almeida, L.M.; Dinis, T.C.; Salvayre, R.; Augé, N. Resveratrol inhibits the mTOR mitogenic signaling evoked by oxidized LDL in smooth muscle cells. Atherosclerosis,  2009, 205(1), 126-134.
[http://dx.doi.org/10.1016/j.atherosclerosis.2008.11.011] [PMID:  19108833] 
[143] 
Szkudelski, T.; Szkudelska, K. Anti-diabetic effects of resveratrol. Ann. N. Y. Acad. Sci.,  2011, 1215, 34-39.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05844.x] [PMID:  21261639] 
[144] 
Arrick, D.M.; Sun, H.; Patel, K.P.; Mayhan, W.G. Chronic resveratrol treatment restores vascular responsiveness of cerebral arterioles in type 1 diabetic rats. Am. J. Physiol. Heart Circ. Physiol.,  2011, 301(3), H696-H703.
[http://dx.doi.org/10.1152/ajpheart.00312.2011] [PMID:  21666113] 
[145] 
Sulaiman, M.; Matta, M.J.; Sunderesan, N.R.; Gupta, M.P.; Periasamy, M.; Gupta, M. Resveratrol, an activator of SIRT1, upregulates sarcoplasmic calcium ATPase and improves cardiac function in diabetic cardiomyopathy. Am. J. Physiol. Heart Circ. Physiol.,  2010, 298(3), H833-H843.
[http://dx.doi.org/10.1152/ajpheart.00418.2009] [PMID:  20008278] 
[146] 
Deng, J.Y.; Hsieh, P.S.; Huang, J.P.; Lu, L.S.; Hung, L.M. Activation of estrogen receptor is crucial for resveratrol-stimulating muscular glucose uptake via both insulin-dependent and -independent pathways. Diabetes,  2008, 57(7), 1814-1823.
[http://dx.doi.org/10.2337/db07-1750] [PMID:  18426865] 
[147] 
Palsamy, P.; Subramanian, S. Modulatory effects of resveratrol on attenuating the key enzymes activities of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. Chem. Biol. Interact.,  2009, 179(2-3), 356-362.
[http://dx.doi.org/10.1016/j.cbi.2008.11.008] [PMID:  19059388] 
[148] 
Vetterli, L.; Brun, T.; Giovannoni, L.; Bosco, D.; Maechler, P. Resveratrol potentiates glucose-stimulated insulin secretion in INS-1E beta-cells and human islets through a SIRT1-dependent mechanism. J. Biol. Chem.,  2011, 286(8), 6049-6060.
[http://dx.doi.org/10.1074/jbc.M110.176842] [PMID:  21163946] 
[149] 
Hardie, D.G.; Pan, D.A. Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase. Biochem. Soc. Trans.,  2002, 30(Pt 6), 1064-1070.
[http://dx.doi.org/10.1042/bst0301064] [PMID:  12440973] 
[150] 
Sun, C.; Zhang, F.; Ge, X.; Yan, T.; Chen, X.; Shi, X.; Zhai, Q. SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab.,  2007, 6(4), 307-319.
[http://dx.doi.org/10.1016/j.cmet.2007.08.014] [PMID:  17908559] 
[151] 
Um, J.H.; Park, S.J.; Kang, H.; Yang, S.; Foretz, M.; McBurney, M.W.; Kim, M.K.; Viollet, B.; Chung, J.H. AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes,  2010, 59(3), 554-563.
[http://dx.doi.org/10.2337/db09-0482] [PMID:  19934007] 
[152] 
Olas, B.; Wachowicz, B.; Saluk-Juszczak, J.; Zieliński, T. Effect of resveratrol, a natural polyphenolic compound, on platelet activation induced by endotoxin or thrombin. Thromb. Res.,  2002, 107(3-4), 141-145.
[http://dx.doi.org/10.1016/S0049-3848(02)00273-6] [PMID:  12431480] 
[153] 
Abe, K.; Tawara, S.; Oi, K.; Hizume, T.; Uwatoku, T.; Fukumoto, Y.; Kaibuchi, K.; Shimokawa, H. Long-term inhibition of Rho-kinase ameliorates hypoxia-induced pulmonary hypertension in mice. J. Cardiovasc. Pharmacol.,  2006, 48(6), 280-285.
[http://dx.doi.org/10.1097/01.fjc.0000248244.64430.4a] [PMID:  17204906] 
[154] 
Bonaventura, A.; Montecucco, F.; Dallegri, F. Cellular recruitment in myocardial ischaemia/reperfusion injury. Eur. J. Clin. Invest.,  2016, 46(6), 590-601.
[http://dx.doi.org/10.1111/eci.12633] [PMID:  27090739] 
[155] 
Montecucco, F.; Carbone, F.; Schindler, T.H. Pathophysiology of ST-segment elevation myocardial infarction: novel mechanisms and treatments. Eur. Heart J.,  2016, 37(16), 1268-1283.
[http://dx.doi.org/10.1093/eurheartj/ehv592] [PMID:  26543047] 
[156] 
Gurusamy, N.; Ray, D.; Lekli, I.; Das, D.K. Red wine antioxidant resveratrol-modified cardiac stem cells regenerate infarcted myocardium. J. Cell. Mol. Med.,  2010, 14(9), 2235-2239.
[http://dx.doi.org/10.1111/j.1582-4934.2010.01140.x] [PMID:  20716127] 
[157] 
Hung, L.M.; Su, M.J.; Chen, J.K. Resveratrol protects myocardial ischemia-reperfusion injury through both NO-dependent and NO-independent mechanisms. Free Radic. Biol. Med.,  2004, 36(6), 774-781.
[http://dx.doi.org/10.1016/j.freeradbiomed.2003.12.016] [PMID:  14990356] 
[158] 
Petrovski, G.; Gurusamy, N.; Das, D.K. Resveratrol in cardiovascular health and disease. Ann. N. Y. Acad. Sci.,  2011, 1215, 22-33.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05843.x] [PMID:  21261638] 
[159] 
Das, S.; Cordis, G.A.; Maulik, N.; Das, D.K. Pharmacological preconditioning with resveratrol: role of CREB-dependent Bcl-2 signaling via adenosine A3 receptor activation. Am. J. Physiol. Heart Circ. Physiol.,  2005, 288(1), H328-H335.
[http://dx.doi.org/10.1152/ajpheart.00453.2004] [PMID:  15345477] 
[160] 
Chen, C.J.; Yu, W.; Fu, Y.C.; Wang, X.; Li, J.L.; Wang, W. Resveratrol protects cardiomyocytes from hypoxia-induced apoptosis through the SIRT1-FoxO1 pathway. Biochem. Biophys. Res. Commun.,  2009, 378(3), 389-393.
[http://dx.doi.org/10.1016/j.bbrc.2008.11.110] [PMID:  19059213] 
[161] 
Gurusamy, N.; Lekli, I.; Mukherjee, S.; Ray, D.; Ahsan, M.K.; Gherghiceanu, M.; Popescu, L.M.; Das, D.K. Cardioprotection by resveratrol: a novel mechanism via autophagy involving the mTORC2 pathway. Cardiovasc. Res.,  2010, 86(1), 103-112.
[http://dx.doi.org/10.1093/cvr/cvp384] [PMID:  19959541] 
[162] 
Chen, Y.R.; Yi, F.F.; Li, X.Y.; Wang, C.Y.; Chen, L.; Yang, X.C.; Su, P.X.; Cai, J. Resveratrol attenuates ventricular arrhythmias and improves the long-term survival in rats with myocardial infarction. Cardiovasc. Drugs Ther.,  2008, 22(6), 479-485.
[http://dx.doi.org/10.1007/s10557-008-6141-8] [PMID:  18853243] 
[163] 
Gu, X.S.; Wang, Z.B.; Ye, Z.; Lei, J.P.; Li, L.; Su, D.F.; Zheng, X. Resveratrol, an activator of SIRT1, upregulates AMPK and improves cardiac function in heart failure. Genet. Mol. Res.,  2014, 13(1), 323-335.
[http://dx.doi.org/10.4238/2014.January.17.17] [PMID:  24535859] 
[164] 
Kanamori, H.; Takemura, G.; Goto, K.; Tsujimoto, A.; Ogino, A.; Takeyama, T.; Kawaguchi, T.; Watanabe, T.; Morishita, K.; Kawasaki, M.; Mikami, A.; Fujiwara, T.; Fujiwara, H.; Seishima, M.; Minatoguchi, S. Resveratrol reverses remodeling in hearts with large, old myocardial infarctions through enhanced autophagy-activating AMP kinase pathway. Am. J. Pathol.,  2013, 182(3), 701-713.
[http://dx.doi.org/10.1016/j.ajpath.2012.11.009] [PMID:  23274061] 
[165] 
Gupta, P.K.; DiPette, D.J.; Supowit, S.C. Protective effect of resveratrol against pressure overload-induced heart failure. Food Sci. Nutr.,  2014, 2(3), 218-229.
[http://dx.doi.org/10.1002/fsn3.92] [PMID:  24936291] 
[166] 
Magyar, K.; Halmosi, R.; Palfi, A.; Feher, G.; Czopf, L.; Fulop, A.; Battyany, I.; Sumegi, B.; Toth, K.; Szabados, E. Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. Clin. Hemorheol. Microcirc.,  2012, 50(3), 179-187.
[PMID:  22240353] 
[167] 
Chan, A.Y.; Dolinsky, V.W.; Soltys, C.L.; Viollet, B.; Baksh, S.; Light, P.E.; Dyck, J.R. Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt. J. Biol. Chem.,  2008, 283(35), 24194-24201.
[http://dx.doi.org/10.1074/jbc.M802869200] [PMID:  18562309] 
[168] 
Carbone, F.; Teixeira, P.C.; Braunersreuther, V.; Mach, F.; Vuilleumier, N.; Montecucco, F. Pathophysiology and treatments of oxidative injury in ischemic stroke: focus on the phagocytic NADPH Oxidase 2. Antioxid. Redox Signal.,  2015, 23(5), 460-489.
[http://dx.doi.org/10.1089/ars.2013.5778] [PMID:  24635113] 
[169] 
Clark, D.; Tuor, U.I.; Thompson, R.; Institoris, A.; Kulynych, A.; Zhang, X.; Kinniburgh, D.W.; Bari, F.; Busija, D.W.; Barber, P.A. Protection against recurrent stroke with resveratrol: endothelial protection. PLoS One,  2012, 7(10)e47792
[http://dx.doi.org/10.1371/journal.pone.0047792] [PMID:  23082218] 
[170] 
Huang, S.S.; Tsai, M.C.; Chih, C.L.; Hung, L.M.; Tsai, S.K. Resveratrol reduction of infarct size in Long-Evans rats subjected to focal cerebral ischemia. Life Sci.,  2001, 69(9), 1057-1065.
[http://dx.doi.org/10.1016/S0024-3205(01)01195-X] [PMID:  11508648] 
[171] 
Singh, N.; Agrawal, M.; Doré, S. Neuroprotective properties and mechanisms of resveratrol in in vitro and in vivo experimental cerebral stroke models. ACS Chem. Neurosci.,  2013, 4(8), 1151-1162.
[http://dx.doi.org/10.1021/cn400094w] [PMID:  23758534] 
[172] 
Wan, D.; Zhou, Y.; Wang, K.; Hou, Y.; Hou, R.; Ye, X. Resveratrol provides neuroprotection by inhibiting phosphodiesterases and regulating the cAMP/AMPK/SIRT1 pathway after stroke in rats. Brain Res. Bull.,  2016, 121, 255-262.
[http://dx.doi.org/10.1016/j.brainresbull.2016.02.011] [PMID:  26876758] 
[173] 
de la Lastra, C.A.; Villegas, I. Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications. Mol. Nutr. Food Res.,  2005, 49(5), 405-430.
[http://dx.doi.org/10.1002/mnfr.200500022] [PMID:  15832402] 
[174] 
Jin, F.; Wu, Q.; Lu, Y.F.; Gong, Q.H.; Shi, J.S. Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson’s disease in rats. Eur. J. Pharmacol.,  2008, 600(1-3), 78-82.
[http://dx.doi.org/10.1016/j.ejphar.2008.10.005] [PMID:  18940189] 
[175] 
Kennedy, D.O.; Wightman, E.L.; Reay, J.L.; Lietz, G.; Okello, E.J.; Wilde, A.; Haskell, C.F. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am. J. Clin. Nutr.,  2010, 91(6), 1590-1597.
[http://dx.doi.org/10.3945/ajcn.2009.28641] [PMID:  20357044] 
[176] 
Wightman, E.L.; Reay, J.L.; Haskell, C.F.; Williamson, G.; Dew, T.P.; Kennedy, D.O. Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: a randomised, double-blind, placebo-controlled, cross-over investigation. Br. J. Nutr.,  2014, 112(2), 203-213.
[http://dx.doi.org/10.1017/S0007114514000737] [PMID:  24804871] 
[177] 
Evans, H.M.; Howe, P.R.; Wong, R.H. Clinical evaluation of effects of chronic resveratrol supplementation on cerebrovascular function, cognition, mood, physical function and general well-being in postmenopausal women-rationale and study design. clinical evaluation of effects of chronic resveratrol supplementation on cerebrovascular function, cognition, mood, physical function and general well-being in postmenopausal women-rationale and study design. Nutrients,  2016, 8(3), 150.
[http://dx.doi.org/10.3390/nu8030150] [PMID:  27005658] 
[178] 
Chen, J.; Bai, Q.; Zhao, Z.; Sui, H.; Xie, X. Resveratrol improves delayed r-tPA treatment outcome by reducing MMPs. Acta Neurol. Scand.,  2016, 134(1), 54-60.
[http://dx.doi.org/10.1111/ane.12511] [PMID:  26455907] 
[179] 
Shao, A.W.; Wu, H.J.; Chen, S.; Ammar, A.B.; Zhang, J.M.; Hong, Y. Resveratrol attenuates early brain injury after subarachnoid hemorrhage through inhibition of NF-κB-dependent inflammatory/MMP-9 pathway. CNS Neurosci. Ther.,  2014, 20(2), 182-185.
[http://dx.doi.org/10.1111/cns.12194] [PMID:  24279692] 
[180] 
Gao, D.; Huang, T.; Jiang, X.; Hu, S.; Zhang, L.; Fei, Z. Resveratrol protects primary cortical neuron cultures from transient oxygen-glucose deprivation by inhibiting MMP-9. Mol. Med. Rep.,  2014, 9(6), 2197-2204.
[http://dx.doi.org/10.3892/mmr.2014.2086] [PMID:  24682241] 
[181] 
Wei, H.; Wang, S.; Zhen, L.; Yang, Q.; Wu, Z.; Lei, X.; Lv, J.; Xiong, L.; Xue, R. Resveratrol attenuates the blood-brain barrier dysfunction by regulation of the MMP-9/TIMP-1 balance after cerebral ischemia reperfusion in rats. J. Mol. Neurosci.,  2015, 55(4), 872-879.
[http://dx.doi.org/10.1007/s12031-014-0441-1] [PMID:  25330860] 
[182] 
Krenz, M.; Korthuis, R.J. Moderate ethanol ingestion and cardiovascular protection: from epidemiologic associations to cellular mechanisms. J. Mol. Cell. Cardiol.,  2012, 52(1), 93-104.
[http://dx.doi.org/10.1016/j.yjmcc.2011.10.011] [PMID:  22041278] 
[183] 
Yusuf, S.; Hawken, S.; Ounpuu, S. Dans, T.; Avezum, A.; Lanas, F.; McQueen, M.; Budaj, A.; Pais, P.; Varigos, J.; Lisheng, L. INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet,  2004, 364(9438), 937-952.
[http://dx.doi.org/10.1016/S0140-6736(04)17018-9] [PMID:  15364185] 
[184] 
Mukamal, K.J.; Jensen, M.K.; Grønbaek, M.; Stampfer, M.J.; Manson, J.E.; Pischon, T.; Rimm, E.B. Drinking frequency, mediating biomarkers, and risk of myocardial infarction in women and men. Circulation,  2005, 112(10), 1406-1413.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.105.537704] [PMID:  16129796] 
[185] 
Mukamal, K.J.; Chiuve, S.E.; Rimm, E.B. Alcohol consumption and risk for coronary heart disease in men with healthy lifestyles. Arch. Intern. Med.,  2006, 166(19), 2145-2150.
[http://dx.doi.org/10.1001/archinte.166.19.2145] [PMID:  17060546] 
[186] 
de Leiris, J.; Besse, S.; Boucher, F. Diet and heart health: moderate wine drinking strengthens the cardioprotective effects of fish consumption. Curr. Pharm. Biotechnol.,  2010, 11(8), 911-921.
[http://dx.doi.org/10.2174/138920110793262024] [PMID:  20874685] 
[187] 
Patra, J.; Taylor, B.; Irving, H.; Roerecke, M.; Baliunas, D.; Mohapatra, S.; Rehm, J. Alcohol consumption and the risk of morbidity and mortality for different stroke types--a systematic review and meta-analysis. BMC Public Health,  2010, 10, 258.
[http://dx.doi.org/10.1186/1471-2458-10-258] [PMID:  20482788] 
[188] 
Djoussé, L.; Gaziano, J.M. Alcohol consumption and heart failure: a systematic review. Curr. Atheroscler. Rep.,  2008, 10(2), 117-120.
[http://dx.doi.org/10.1007/s11883-008-0017-z] [PMID:  18417065] 
[189] 
Puddey, I.B.; Zilkens, R.R.; Croft, K.D.; Beilin, L.J. Alcohol and endothelial function: a brief review. Clin. Exp. Pharmacol. Physiol.,  2001, 28(12), 1020-1024.
[http://dx.doi.org/10.1046/j.1440-1681.2001.03572.x] [PMID:  11903307] 
[190] 
Abou-Agag, L.H.; Khoo, N.K.; Binsack, R.; White, C.R.; Darley-Usmar, V.; Grenett, H.E.; Booyse, F.M.; Digerness, S.B.; Zhou, F.; Parks, D.A. Evidence of cardiovascular protection by moderate alcohol: role of nitric oxide. Free Radic. Biol. Med.,  2005, 39(4), 540-548.
[http://dx.doi.org/10.1016/j.freeradbiomed.2005.04.007] [PMID:  16043025] 
[191] 
Gazzieri, D.; Trevisani, M.; Tarantini, F.; Bechi, P.; Masotti, G.; Gensini, G.F.; Castellani, S.; Marchionni, N.; Geppetti, P.; Harrison, S. Ethanol dilates coronary arteries and increases coronary flow via transient receptor potential vanilloid 1 and calcitonin gene-related peptide. Cardiovasc. Res.,  2006, 70(3), 589-599.
[http://dx.doi.org/10.1016/j.cardiores.2006.02.027] [PMID:  16579978] 
[192] 
Carbone, F.; Montecucco, F. Inflammation in arterial diseases. IUBMB Life,  2015, 67(1), 18-28.
[http://dx.doi.org/10.1002/iub.1344] [PMID:  25631520] 
[193] 
Badía, E.; Sacanella, E.; Fernández-Solá, J.; Nicolás, J.M.; Antúnez, E.; Rotilio, D.; de Gaetano, G.; Urbano-Márquez, A.; Estruch, R. Decreased tumor necrosis factor-induced adhesion of human monocytes to endothelial cells after moderate alcohol consumption. Am. J. Clin. Nutr.,  2004, 80(1), 225-230.
[http://dx.doi.org/10.1093/ajcn/80.1.225] [PMID:  15213052] 
[194] 
Kiviniemi, T.O.; Saraste, A.; Toikka, J.O.; Saraste, M.; Raitakari, O.T.; Pärkkä, J.P.; Lehtimäki, T.; Hartiala, J.J.; Viikari, J.; Koskenvuo, J.W. A moderate dose of red wine, but not de-alcoholized red wine increases coronary flow reserve. Atherosclerosis,  2007, 195(2), e176-e181.
[http://dx.doi.org/10.1016/j.atherosclerosis.2007.06.004] [PMID:  17662293] 
[195] 
Tousoulis, D.; Ntarladimas, I.; Antoniades, C.; Vasiliadou, C.; Tentolouris, C.; Papageorgiou, N.; Latsios, G.; Stefanadis, C. Acute effects of different alcoholic beverages on vascular endothelium, inflammatory markers and thrombosis fibrinolysis system. Clin. Nutr.,  2008, 27(4), 594-600.
[http://dx.doi.org/10.1016/j.clnu.2008.01.002] [PMID:  18295937] 
[196] 
Suzuki, K.; Elkind, M.S.; Boden-Albala, B.; Jin, Z.; Berry, G.; Di Tullio, M.R.; Sacco, R.L.; Homma, S. Moderate alcohol consumption is associated with better endothelial function: a cross sectional study. BMC Cardiovasc. Disord.,  2009, 9, 8.
[http://dx.doi.org/10.1186/1471-2261-9-8] [PMID:  19228434] 
[197] 
Vasdev, S.; Ford, C.A.; Longerich, L.; Parai, S.; Gadag, V. Antihypertensive effect of low ethanol intake in spontaneously hypertensive rats. Mol. Cell. Biochem.,  1999, 200(1-2), 85-92.
[http://dx.doi.org/10.1023/A:1006950414560] [PMID:  10569187] 
[198] 
Briasoulis, A.; Agarwal, V.; Messerli, F.H. Alcohol consumption and the risk of hypertension in men and women: a systematic review and meta-analysis. J. Clin. Hypertens. (Greenwich),  2012, 14(11), 792-798.
[http://dx.doi.org/10.1111/jch.12008] [PMID:  23126352] 
[199] 
Gardner, C.D.; Tribble, D.L.; Young, D.R.; Ahn, D.; Fortmann, S.P. Associations of HDL, HDL. Associations of HDL, HDL(2), and HDL(3) cholesterol and apolipoproteins A-I and B with lifestyle factors in healthy women and men: the Stanford Five City Project. Prev. Med.,  2000, 31(4), 346-356.
[http://dx.doi.org/10.1006/pmed.2000.0716] [PMID:  11006059] 
[200] 
Brinton, E.A. Effects of ethanol intake on lipoproteins. Curr. Atheroscler. Rep.,  2012, 14(2), 108-114.
[http://dx.doi.org/10.1007/s11883-012-0230-7] [PMID:  22350634] 
[201] 
Perret, B.; Ruidavets, J.B.; Vieu, C.; Jaspard, B.; Cambou, J.P.; Terce, F.; Collet, X. Alcohol consumption is associated with enrichment of high-density lipoprotein particles in polyunsaturated lipids and increased cholesterol esterification rate. Alcohol. Clin. Exp. Res.,  2002, 26(8), 1134-1140.
[http://dx.doi.org/10.1111/j.1530-0277.2002.tb02649.x] [PMID:  12198387] 
[202] 
Sierksma, A.; Vermunt, S.H.; Lankhuizen, I.M.; van der Gaag, M.S.; Scheek, L.M.; Grobbee, D.E.; van Tol, A.; Hendriks, H.F. Effect of moderate alcohol consumption on parameters of reverse cholesterol transport in postmenopausal women. Alcohol. Clin. Exp. Res.,  2004, 28(4), 662-666.
[http://dx.doi.org/10.1097/01.ALC.0000122763.30770.F5] [PMID:  15100619] 
[203] 
Beulens, J.W.; Sierksma, A.; van Tol, A.; Fournier, N.; van Gent, T.; Paul, J.L.; Hendriks, H.F. Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1. J. Lipid Res.,  2004, 45(9), 1716-1723.
[http://dx.doi.org/10.1194/jlr.M400109-JLR200] [PMID:  15231854] 
[204] 
Hoang, A.; Tefft, C.; Duffy, S.J.; Formosa, M.; Henstridge, D.C.; Kingwell, B.A.; Sviridov, D. ABCA1 expression in humans is associated with physical activity and alcohol consumption. Atherosclerosis,  2008, 197(1), 197-203.
[http://dx.doi.org/10.1016/j.atherosclerosis.2007.03.017] [PMID:  17481640] 
[205] 
Liisanantti, M.K.; Savolainen, M.J. Phosphatidylethanol mediates its effects on the vascular endothelial growth factor via HDL receptor in endothelial cells. Alcohol. Clin. Exp. Res.,  2009, 33(2), 283-288.
[http://dx.doi.org/10.1111/j.1530-0277.2008.00831.x] [PMID:  19032580] 
[206] 
Hannuksela, M.L.; Rämet, M.E.; Nissinen, A.E.; Liisanantti, M.K.; Savolainen, M.J. Effects of ethanol on lipids and atherosclerosis. Pathophysiology,  2004, 10(2), 93-103.
[http://dx.doi.org/10.1016/j.pathophys.2003.10.009] [PMID:  15006415] 
[207] 
Wakabayashi, I.; Groschner, K. Modification of the association between alcohol drinking and non-HDL cholesterol by gender. Clin. Chim. Acta,  2009, 404(2), 154-159.
[http://dx.doi.org/10.1016/j.cca.2009.03.047] [PMID:  19336233] 
[208] 
Tolstrup, J.S.; Grønbaek, M.; Nordestgaard, B.G. Alcohol intake, myocardial infarction, biochemical risk factors, and alcohol dehydrogenase genotypes. Circ Cardiovasc Genet,  2009, 2(5), 507-514.
[http://dx.doi.org/10.1161/CIRCGENETICS.109.873604] [PMID:  20031627] 
[209] 
Perissinotto, E.; Buja, A.; Maggi, S.; Enzi, G.; Manzato, E.; Scafato, E.; Mastrangelo, G.; Frigo, A.C.; Coin, A.; Crepaldi, G.; Sergi, G.; Group, I.W. ILSA Working Group. Alcohol consumption and cardiovascular risk factors in older lifelong wine drinkers: The Italian Longitudinal Study on Aging. Nutr. Metab. Cardiovasc. Dis.,  2010, 20(9), 647-655.
[http://dx.doi.org/10.1016/j.numecd.2009.05.014] [PMID:  19695851] 
[210] 
Yin, R.X.; Li, Y.Y.; Liu, W.Y.; Zhang, L.; Wu, J.Z. Interactions of the apolipoprotein A5 gene polymorphisms and alcohol consumption on serum lipid levels. PLoS One,  2011, 6(3)e17954
[http://dx.doi.org/10.1371/journal.pone.0017954] [PMID:  21423763] 
[211] 
Corella, D.; Portolés, O.; Arriola, L.; Chirlaque, M.D.; Barrricarte, A.; Francés, F.; Huerta, J.M.; Larrañaga, N.; Martínez, C.; Martinez-Camblor, P.; Molina, E.; Navarro, C.; Quirós, J.R.; Rodríguez, L.; Sánchez, M.J.; Ros, E.; Sala, N.; González, C.A.; Moreno-Iribas, C. Saturated fat intake and alcohol consumption modulate the association between the APOE polymorphism and risk of future coronary heart disease: a nested case-control study in the Spanish EPIC cohort. J. Nutr. Biochem.,  2011, 22(5), 487-494.
[http://dx.doi.org/10.1016/j.jnutbio.2010.04.003] [PMID:  20688498] 
[212] 
Wang, Z.; Yao, T.; Song, Z. Chronic alcohol consumption disrupted cholesterol homeostasis in rats: down-regulation of low-density lipoprotein receptor and enhancement of cholesterol biosynthesis pathway in the liver. Alcohol. Clin. Exp. Res.,  2010, 34(3), 471-478.
[http://dx.doi.org/10.1111/j.1530-0277.2009.01111.x] [PMID:  20028367] 
[213] 
Ruixing, Y.; Yiyang, L.; Meng, L.; Kela, L.; Xingjiang, L.; Lin, Z.; Wanying, L.; Jinzhen, W.; Dezhai, Y.; Weixiong, L. Interactions of the apolipoprotein C-III 3238C>G polymorphism and alcohol consumption on serum triglyceride levels. Lipids Health Dis.,  2010, 9, 86.
[PMID:  20716347] 
[214] 
Pietraszek, A.; Gregersen, S.; Hermansen, K. Alcohol and type 2 diabetes. A review. Nutr. Metab. Cardiovasc. Dis.,  2010, 20(5), 366-375.
[http://dx.doi.org/10.1016/j.numecd.2010.05.001] [PMID:  20556883] 
[215] 
Baliunas, D.O.; Taylor, B.J.; Irving, H.; Roerecke, M.; Patra, J.; Mohapatra, S.; Rehm, J. Alcohol as a risk factor for type 2 diabetes: A systematic review and meta-analysis. Diabetes Care,  2009, 32(11), 2123-2132.
[http://dx.doi.org/10.2337/dc09-0227] [PMID:  19875607] 
[216] 
Schrieks, I.C.; Heil, A.L.J.; Hendriks, H.F.J.; Mukamal, K.J.; Beulens, J.W.J. The effect of alcohol consumption on insulin sensitivity and glycemic status: a systematic review and meta-analysis of intervention studies. Diabetes Care,  2015, 38(4), 723-732.
[PMID:  25805864] 
[217] 
Lieber, C.S. Alcohol and the liver: 1984 update. Hepatology,  1984, 4(6), 1243-1260.
[http://dx.doi.org/10.1002/hep.1840040625] [PMID:  6389304] 
[218] 
Sierksma, A.; Patel, H.; Ouchi, N.; Kihara, S.; Funahashi, T.; Heine, R.J.; Grobbee, D.E.; Kluft, C.; Hendriks, H.F. Effect of moderate alcohol consumption on adiponectin, tumor necrosis factor-alpha, and insulin sensitivity. Diabetes Care,  2004, 27(1), 184-189.
[http://dx.doi.org/10.2337/diacare.27.1.184] [PMID:  14693987] 
[219] 
Carbone, F.; Mach, F.; Montecucco, F. The role of adipocytokines in atherogenesis and atheroprogression. Curr. Drug Targets,  2015, 16(4), 295-320.
[http://dx.doi.org/10.2174/1389450115666141109213439] [PMID:  25382206] 
[220] 
Ruan, H.; Dong, L.Q. Adiponectin signaling and function in insulin target tissues. J. Mol. Cell Biol.,  2016, 8(2), 101-109.
[http://dx.doi.org/10.1093/jmcb/mjw014] [PMID:  26993044] 
[221] 
Imhof, A.; Froehlich, M.; Brenner, H.; Boeing, H.; Pepys, M.B.; Koenig, W. Effect of alcohol consumption on systemic markers of inflammation. Lancet,  2001, 357(9258), 763-767.
[http://dx.doi.org/10.1016/S0140-6736(00)04170-2] [PMID:  11253971] 
[222] 
Sierksma, A.; van der Gaag, M.S.; Kluft, C.; Hendriks, H.F. Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels; a randomized, diet-controlled intervention study. Eur. J. Clin. Nutr.,  2002, 56(11), 1130-1136.
[http://dx.doi.org/10.1038/sj.ejcn.1601459] [PMID:  12428180] 
[223] 
Albert, M.A.; Glynn, R.J.; Ridker, P.M. Alcohol consumption and plasma concentration of C-reactive protein. Circulation,  2003, 107(3), 443-447.
[http://dx.doi.org/10.1161/01.CIR.0000045669.16499.EC] [PMID:  12551869] 
[224] 
Wandler, A.; Bruun, J.M.; Nielsen, M.P.; Richelsen, B. Ethanol exerts anti-inflammatory effects in human adipose tissue in vitro. Mol. Cell. Endocrinol,  2008, 296(1-2), 26-31.
[http://dx.doi.org/10.1016/j.mce.2008.09.006] [PMID:  18840498] 
[225] 
Miceli, M.; Alberti, L.; Bennardini, F.; Di Simplicio, P.; Seghieri, G.; Rao, G.H.; Franconi, F. Effect of low doses of ethanol on platelet function in long-life abstainers and moderate-wine drinkers. Life Sci.,  2003, 73(12), 1557-1566.
[http://dx.doi.org/10.1016/S0024-3205(03)00473-9] [PMID:  12865095] 
[226] 
Estruch, R.; Sacanella, E.; Mota, F.; Chiva-Blanch, G.; Antúnez, E.; Casals, E.; Deulofeu, R.; Rotilio, D.; Andres-Lacueva, C.; Lamuela-Raventos, R.M.; de Gaetano, G.; Urbano-Marquez, A. Moderate consumption of red wine, but not gin, decreases erythrocyte superoxide dismutase activity: a randomised cross-over trial. Nutr. Metab. Cardiovasc. Dis.,  2011, 21(1), 46-53.
[http://dx.doi.org/10.1016/j.numecd.2009.07.006] [PMID:  19819677] 
[227] 
Jensen, T.; Retterstøl, L.J.; Sandset, P.M.; Godal, H.C.; Skjønsberg, O.H. A daily glass of red wine induces a prolonged reduction in plasma viscosity: a randomized controlled trial. Blood Coagul. Fibrinolysis,  2006, 17(6), 471-476.
[http://dx.doi.org/10.1097/01.mbc.0000240920.72930.63] [PMID:  16905951] 
[228] 
Pieters, M.; Vorster, H.H.; Jerling, J.C.; Venter, C.S.; Kotze, R.C.; Bornman, E.; Malfliet, J.J.; Rijken, D.C. The effect of ethanol and its metabolism on fibrinolysis. Thromb. Haemost.,  2010, 104(4), 724-733.
[PMID:  20664891] 
[229] 
Reynolds, K.; Lewis, B.; Nolen, J.D.; Kinney, G.L.; Sathya, B.; He, J. Alcohol consumption and risk of stroke: a meta-analysis. JAMA,  2003, 289(5), 579-588.
[http://dx.doi.org/10.1001/jama.289.5.579] [PMID:  12578491] 
[230] 
Pomp, E.R.; Rosendaal, F.R.; Doggen, C.J. Alcohol consumption is associated with a decreased risk of venous thrombosis. Thromb. Haemost.,  2008, 99(1), 59-63.
[http://dx.doi.org/10.1160/TH07-07-0470] [PMID:  18217135] 
[231] 
Miyamae, M.; Rodriguez, M.M.; Camacho, S.A.; Diamond, I.; Mochly-Rosen, D.; Figueredo, V.M. Activation of epsilon protein kinase C correlates with a cardioprotective effect of regular ethanol consumption. Proc. Natl. Acad. Sci. USA,  1998, 95(14), 8262-8267.
[http://dx.doi.org/10.1073/pnas.95.14.8262] [PMID:  9653175] 
[232] 
Zhou, H.Z.; Karliner, J.S.; Gray, M.O. Moderate alcohol consumption induces sustained cardiac protection by activating PKC-epsilon and Akt. Am. J. Physiol. Heart Circ. Physiol.,  2002, 283(1), H165-H174.
[http://dx.doi.org/10.1152/ajpheart.00408.2001] [PMID:  12063287] 
[233] 
Zhu, P.; Zhou, H.Z.; Gray, M.O. Chronic ethanol-induced myocardial protection requires activation of mitochondrial K(ATP) channels. J. Mol. Cell. Cardiol.,  2000, 32(11), 2091-2095.
[http://dx.doi.org/10.1006/jmcc.2000.1233] [PMID:  11040112] 
[234] 
Yang, X.; Cohen, M.V.; Downey, J.M. Mechanism of cardioprotection by early ischemic preconditioning. Cardiovasc. Drugs Ther.,  2010, 24(3), 225-234.
[http://dx.doi.org/10.1007/s10557-010-6236-x] [PMID:  20505987] 
[235] 
Hausenloy, D.J.; Yellon, D.M. The second window of preconditioning (SWOP) where are we now? Cardiovasc. Drugs Ther.,  2010, 24(3), 235-254.
[http://dx.doi.org/10.1007/s10557-010-6237-9] [PMID:  20496105] 
[236] 
Chen, C.H.; Budas, G.R.; Churchill, E.N.; Disatnik, M.H.; Hurley, T.D.; Mochly-Rosen, D. Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science,  2008, 321(5895), 1493-1495.
[http://dx.doi.org/10.1126/science.1158554] [PMID:  18787169] 
[237] 
Dayton, C.; Yamaguchi, T.; Kamada, K.; Carter, P.; Korthuis, R.J. Antecedent ethanol ingestion prevents postischemic leukocyte adhesion and P-selectin expression by a protein kinase C-dependent mechanism. Dig. Dis. Sci.,  2005, 50(4), 684-690.
[http://dx.doi.org/10.1007/s10620-005-2557-1] [PMID:  15844702] 
[238] 
Yamaguchi, T.; Dayton, C.; Shigematsu, T.; Carter, P.; Yoshikawa, T.; Gute, D.C.; Korthuis, R.J. Preconditioning with ethanol prevents postischemic leukocyte-endothelial cell adhesive interactions. Am. J. Physiol. Heart Circ. Physiol.,  2002, 283(3), H1019-H1030.
[http://dx.doi.org/10.1152/ajpheart.00173.2002] [PMID:  12181132] 
[239] 
Gaskin, F.S.; Kamada, K.; Yusof, M.; Durante, W.; Gross, G.; Korthuis, R.J. AICAR preconditioning prevents postischemic leukocyte rolling and adhesion: role of K(ATP) channels and heme oxygenase. Microcirculation,  2009, 16(2), 167-176.
[http://dx.doi.org/10.1080/10739680802355897] [PMID:  19152177] 
[240] 
Rakotovao, A.; Berthonneche, C.; Guiraud, A.; de Lorgeril, M.; Salen, P.; de Leiris, J.; Boucher, F. Ethanol, wine, and experimental cardioprotection in ischemia/reperfusion: role of the prooxidant/antioxidant balance. Antioxid. Redox Signal.,  2004, 6(2), 431-438.
[http://dx.doi.org/10.1089/152308604322899503] [PMID:  15025945] 
[241] 
Churchill, E.N.; Disatnik, M.H.; Mochly-Rosen, D. Time-dependent and ethanol-induced cardiac protection from ischemia mediated by mitochondrial translocation of varepsilonPKC and activation of aldehyde dehydrogenase 2. J. Mol. Cell. Cardiol.,  2009, 46(2), 278-284.
[http://dx.doi.org/10.1016/j.yjmcc.2008.09.713] [PMID:  18983847] 
[242] 
Yamaguchi, T.; Kamada, K.; Dayton, C.; Gaskin, F.S.; Yusof, M.; Yoshikawa, T.; Carter, P.; Korthuis, R.J. Role of eNOS-derived NO in the postischemic anti-inflammatory effects of antecedent ethanol ingestion in murine small intestine. Am. J. Physiol. Heart Circ. Physiol.,  2007, 292(3), H1435-H1442.
[http://dx.doi.org/10.1152/ajpheart.00282.2006] [PMID:  17098834] 
[243] 
de Gaetano, G.; Di Castelnuovo, A.; Rotondo, S.; Iacoviello, L.; Donati, M.B. A meta-analysis of studies on wine and beer and cardiovascular disease. Pathophysiol. Haemost. Thromb.,  2002, 32(5-6), 353-355.
[http://dx.doi.org/10.1159/000073598] [PMID:  13679674] 
[244] 
Costanzo, S.; Di Castelnuovo, A.; Donati, M.B.; Iacoviello, L.; de Gaetano, G. Wine, beer or spirit drinking in relation to fatal and non-fatal cardiovascular events: a meta-analysis. Eur. J. Epidemiol.,  2011, 26(11), 833-850.
[http://dx.doi.org/10.1007/s10654-011-9631-0] [PMID:  22076059] 
[245] 
Rimm, E.B.; Klatsky, A.; Grobbee, D.; Stampfer, M.J. Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits. BMJ,  1996, 312(7033), 731-736.
[http://dx.doi.org/10.1136/bmj.312.7033.731] [PMID:  8605457] 
[246] 
Brien, S.E.; Ronksley, P.E.; Turner, B.J.; Mukamal, K.J.; Ghali, W.A. Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies. BMJ,  2011, 342, d636.
[http://dx.doi.org/10.1136/bmj.d636] [PMID:  21343206] 
[247] 
Ronksley, P.E.; Brien, S.E.; Turner, B.J.; Mukamal, K.J.; Ghali, W.A. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ,  2011, 342, d671.
[http://dx.doi.org/10.1136/bmj.d671] [PMID:  21343207] 
[248] 
Conigrave, K.M.; Hu, B.F.; Camargo, C.A., Jr; Stampfer, M.J.; Willett, W.C.; Rimm, E.B. A prospective study of drinking patterns in relation to risk of type 2 diabetes among men. Diabetes,  2001, 50(10), 2390-2395.
[http://dx.doi.org/10.2337/diabetes.50.10.2390] [PMID:  11574424] 
[249] 
Mukamal, K.J.; Conigrave, K.M.; Mittleman, M.A.; Camargo, C.A., Jr; Stampfer, M.J.; Willett, W.C.; Rimm, E.B. Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men. N. Engl. J. Med.,  2003, 348(2), 109-118.
[http://dx.doi.org/10.1056/NEJMoa022095] [PMID:  12519921] 
[250] 
Stranges, S.; Wu, T.; Dorn, J.M.; Freudenheim, J.L.; Muti, P.; Farinaro, E.; Russell, M.; Nochajski, T.H.; Trevisan, M. Relationship of alcohol drinking pattern to risk of hypertension: a population-based study. Hypertension,  2004, 44(6), 813-819.
[http://dx.doi.org/10.1161/01.HYP.0000146537.03103.f2] [PMID:  15477381] 
[251] 
Della Valle, E.; Stranges, S.; Trevisan, M.; Krogh, V.; Fusconi, E.; Dorn, J.M.; Farinaro, E. Drinking habits and health in Northern Italian and American men. Nutr. Metab. Cardiovasc. Dis.,  2009, 19(2), 115-122.
[http://dx.doi.org/10.1016/j.numecd.2008.03.006] [PMID:  18678475] 
[252] 
Whelan, A.P.; Sutherland, W.H.; McCormick, M.P.; Yeoman, D.J.; de Jong, S.A.; Williams, M.J. Effects of white and red wine on endothelial function in subjects with coronary artery disease. Intern. Med. J.,  2004, 34(5), 224-228.
[http://dx.doi.org/10.1111/j.1444-0903.2004.00507.x] [PMID:  15151666] 
[253] 
Lekakis, J.; Rallidis, L.S.; Andreadou, I.; Vamvakou, G.; Kazantzoglou, G.; Magiatis, P.; Skaltsounis, A.L.; Kremastinos, D.T. Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. Eur. J. Cardiovasc. Prev. Rehabil.,  2005, 12(6), 596-600.
[http://dx.doi.org/10.1097/00149831-200512000-00013] [PMID:  16319551] 
[254] 
Karatzi, K.N.; Papamichael, C.M.; Karatzis, E.N.; Papaioannou, T.G.; Aznaouridis, K.A.; Katsichti, P.P.; Stamatelopoulos, K.S.; Zampelas, A.; Lekakis, J.P.; Mavrikakis, M.E. Red wine acutely induces favorable effects on wave reflections and central pressures in coronary artery disease patients. Am. J. Hypertens.,  2005, 18(9 Pt 1), 1161-1167.
[http://dx.doi.org/10.1016/j.amjhyper.2005.03.744] [PMID:  16182104] 
[255] 
Guarda, E.; Godoy, I.; Foncea, R.; Pérez, D.D.; Romero, C.; Venegas, R.; Leighton, F. Red wine reduces oxidative stress in patients with acute coronary syndrome. Int. J. Cardiol.,  2005, 104(1), 35-38.
[http://dx.doi.org/10.1016/j.ijcard.2004.10.013] [PMID:  16137507] 
[256] 
Marinaccio, L.; Lanza, G.A.; Niccoli, G.; Fabretti, A.; Lamendola, P.; Barone, L.; Di Monaco, A.; Di Clemente, F.; Crea, F. Effect of low doses of alcohol on the warm-up phenomenon in patients with stable angina pectoris. Am. J. Cardiol.,  2008, 102(2), 146-149.
[http://dx.doi.org/10.1016/j.amjcard.2008.03.025] [PMID:  18602511] 
[257] 
Tresserra-Rimbau, A.; Medina-Remón, A.; Lamuela-Raventós, R.M.; Bulló, M.; Salas-Salvadó, J.; Corella, D.; Fitó, M.; Gea, A.; Gómez-Gracia, E.; Lapetra, J.; Arós, F.; Fiol, M.; Ros, E.; Serra-Majem, L.; Pintó, X.; Muñoz, M.A.; Estruch, R.; Investigators, P.S. PREDIMED Study Investigators. Moderate red wine consumption is associated with a lower prevalence of the metabolic syndrome in the PREDIMED population. Br. J. Nutr.,  2015, 113(Suppl. 2), S121-S130.
[http://dx.doi.org/10.1017/S0007114514003262] [PMID:  26148915] 
[258] 
Chiva-Blanch, G.; Urpi-Sarda, M.; Ros, E.; Valderas-Martinez, P.; Casas, R.; Arranz, S.; Guillén, M.; Lamuela-Raventós, R.M.; Llorach, R.; Andres-Lacueva, C.; Estruch, R. Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid profile: a randomized clinical trial. Clin. Nutr.,  2013, 32(2), 200-206.
[http://dx.doi.org/10.1016/j.clnu.2012.08.022] [PMID:  22999066] 
[259] 
Gepner, Y.; Golan, R.; Harman-Boehm, I.; Henkin, Y.; Schwarzfuchs, D.; Shelef, I.; Durst, R.; Kovsan, J.; Bolotin, A.; Leitersdorf, E.; Shpitzen, S.; Balag, S.; Shemesh, E.; Witkow, S.; Tangi-Rosental, O.; Chassidim, Y.; Liberty, I.F.; Sarusi, B.; Ben-Avraham, S.; Helander, A.; Ceglarek, U.; Stumvoll, M.; Blüher, M.; Thiery, J.; Rudich, A.; Stampfer, M.J.; Shai, I. Effects of initiating moderate alcohol intake on cardiometabolic risk in adults with type 2 diabetes: a 2-year randomized, controlled trial. Ann. Intern. Med.,  2015, 163(8), 569-579.
[http://dx.doi.org/10.7326/M14-1650] [PMID:  26458258] 
[260] 
Fernández-Jarne, E.; Martínez-Losa, E.; Serrano-Martínez, M.; Prado-Santamaría, M.; Brugarolas-Brufau, C.; Martínez-González, M.A. Type of alcoholic beverage and first acute myocardial infarction: a case-control study in a Mediterranean country. Clin. Cardiol.,  2003, 26(7), 313-318.
[http://dx.doi.org/10.1002/clc.4950260704] [PMID:  12862296] 
[261] 
Marfella, R.; Cacciapuoti, F.; Siniscalchi, M.; Sasso, F.C.; Marchese, F.; Cinone, F.; Musacchio, E.; Marfella, M.A.; Ruggiero, L.; Chiorazzo, G.; Liberti, D.; Chiorazzo, G.; Nicoletti, G.F.; Sardu, C.; D’Andrea, F.; Ammendola, C.; Verza, M.; Coppola, L. Effect of moderate red wine intake on cardiac prognosis after recent acute myocardial infarction of subjects with Type 2 diabetes mellitus. Diabet. Med.,  2006, 23(9), 974-981.
[http://dx.doi.org/10.1111/j.1464-5491.2006.01886.x] [PMID:  16922703] 
[262] 
Oliveira, A.; Lopes, C.; Rodríguez-Artalejo, F. Adherence to the Southern European Atlantic Diet and occurrence of nonfatal acute myocardial infarction. Am. J. Clin. Nutr.,  2010, 92(1), 211-217.
[http://dx.doi.org/10.3945/ajcn.2009.29075] [PMID:  20484454] 
[263] 
Levantesi, G.; Marfisi, R.; Mozaffarian, D.; Franzosi, M.G.; Maggioni, A.; Nicolosi, G.L.; Schweiger, C.; Silletta, M.; Tavazzi, L.; Tognoni, G.; Marchioli, R. Wine consumption and risk of cardiovascular events after myocardial infarction: results from the GISSI-Prevenzione trial. Int. J. Cardiol.,  2013, 163(3), 282-287.
[http://dx.doi.org/10.1016/j.ijcard.2011.06.053] [PMID:  21737162] 
[264] 
Cosmi, F.; Di Giulio, P.; Masson, S.; Finzi, A.; Marfisi, R.M.; Cosmi, D.; Scarano, M.; Tognoni, G.; Maggioni, A.P.; Porcu, M.; Boni, S.; Cutrupi, G.; Tavazzi, L.; Latini, R. GISSI-HF Investigators. Regular wine consumption in chronic heart failure: impact on outcomes, quality of life, and circulating biomarkers. Circ Heart Fail,  2015, 8(3), 428-437.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.114.002091] [PMID:  25925415] 
[265] 
Hernandez-Hernandez, A.; Gea, A.; Ruiz-Canela, M.; Toledo, E.; Beunza, J.J.; Bes-Rastrollo, M.; Martinez-Gonzalez, M.A. Mediterranean alcohol-drinking pattern and the incidence of cardiovascular disease and cardiovascular mortality: The SUN Project. Nutrients,  2015, 7(11), 9116-9126.
[http://dx.doi.org/10.3390/nu7115456] [PMID:  26556367] 
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DOI https://dx.doi.org/10.2174/0929867324666170518100606	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Impact of Red Wine Consumption on Cardiovascular Health

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